EP4 ANTAGONISTS AND USES THEREOF TECHNICAL FIELD OF THE INVENTION [0001] The present invention relates to EP4 antagonists, and uses thereof for treating a proliferative disorder. BACKGROUND OF THE INVENTION [0002] Prostaglandins are mediators of pain, fever and other symptoms associated with inflammation. Prostaglandin E2 (PGE2) is the predominant eicosanoid detected in inflammation conditions. In addition, it is also involved in various physiological and/or pathological conditions such as cancer, hyperalgesia, uterine contraction, digestive peristalsis, awakeness, suppression of gastric acid secretion, blood pressure, platelet function, bone metabolism, angiogenesis or the like. [0003] Four PGE2 receptor subtypes (EP1, EP2, EP3 and EP4) displaying different pharmacological properties exist. The EP4 subtype, a Gs-coupled receptor, stimulates cAMP production, as well as PI3K and GSK3 ^ signaling, and is distributed in a wide variety of tissues, suggesting a major role in PGE ₂ -mediated biological events Various EP4 antagonists have been described previously, for example, in WO 2002/032900, WO 2005/021508, US 6,710,054, and US 7,238,714, the contents of which are incorporated herein by reference in their entireties. SUMMARY OF THE INVENTION [0004] As described herein, the inventors have discovered that levels of urinary PGEM are indicative of patient responsiveness to treatment with an EP4 antagonist. PGE ₂ is a major cyclooxygenase (COX) product that is important in human physiology and pathophysiology that is synthesized downstream of COX-1 and COX-2. “PGEM” or 11α-hydroxy-9,15-dioxo-2,3,4,5- tetranor-prostane-1,20-dioic acid, is the major urinary metabolite of PGE ₂ . EP4 antagonists act to reduce or attenuate the effects of PGE2 signaling via the EP4 receptor, such as reduction of cAMP production, as well as PI3K and GSK3 β signaling. As shown herein, urinary PGEM levels can be used, for example, to predict efficacy of treatments using EP4 antagonists and for patient selection purposes. [0005] Accordingly, provided herein are methods for predicting the efficacy of treatments using EP4 antagonists and/or selecting a patient for application or administration of a treatment comprising an EP4 antagonist. Such methods comprise, in part, methods of identifying patients having elevated urinary concentrations of PGEM, and methods for treating patients having elevated urinary concentrations of PGEM using EP4 antagonists. [0006] In one aspect, the present invention provides a method of identifying or selecting a patient having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of the patient. Such methods can comprise, for example, using an LC–MS/MS method as described herein, and selecting a patient having an elevated concentration of PGEM in the urine sample. [0007] In another aspect, provided herein is a method of treating a proliferative disorder in a patient having or identified as having an elevated urinary concentration of PGEM, for example, as determined using a method described herein, comprising administering to the patient a therapeutically effective amount of an EP4 antagonist. [0008] In another aspect, the present invention provides a method of treating a patient having a proliferative disorder, comprising selecting a patient having an elevated urinary concentration of PGEM, for example, using a method as described herein, and administering to the patient a therapeutically effective amount of an EP4 antagonist. [0009] In some embodiments, a proliferative disorder is a cancer. In some embodiments, an EP4 antagonist is selected from those as described herein. BRIEF DESCRIPTION OF FIGURES [0010] FIG.1 depicts PGE ₂ metabolism. [0011] FIG.2 depicts (A): urinary concentrations of PGE-M of certain patients in study #1, and (B): urinary concentrations of PGE-M of all the patients in study #1. The dashed lines indicate the median concentrations for male patients, female patients, and CRC patients, respectively. The term “CR” indicates that a patient had a complete response; the term “PR” indicates that a patient had a partial response; and the term “mixed response” indicates that a patient had a mixed response. [0012] FIG.3 depicts urinary concentrations of PGE-M of all patients in study #2. DETAILED DESCRIPTION OF THE INVENTION 1. General Description of Certain Embodiments of the Invention [0013] As shown herein, it has been found that there is a correlation between a patient’s urinary concentration of PGEM and the likelihood that the patient will benefit from or be responsive to treatment with an EP4 antagonist. Without wishing to be bound by any particular theory or mechanism, as described herein, the inventors have discovered that a patient having an elevated urinary concentration of PGEM is more likely to benefit from an EP4 antagonist treatment. [0014] PGEM is the major urinary metabolite of PGE2. PGE2 is a cyclooxygenase (COX) product biosynthesized from arachidonic acid by the cyclooxygenases COX-1 and COX-2 and PGE synthases. PGEM levels in urine can be used as an indirect indicator of systemic PGE2 levels given the stability of this analyte. PGE2 can signal via the G-protein coupled receptor (GPCR) EP4. Signaling via the EP4 receptor leads to cAMP production, as well as PI3K and GSK3 ^ signaling. In cancer, PGE ₂ establishes an immunosuppressive tumor microenvironment by binding to EP4, which is expressed on an array of immune cells. The relationship between urinary PGEM and cancer risk have been reported in some retrospective exploratory analyses. These data suggest that urinary PGEM levels are associated with the risk of, or poor prognosis of, colorectal cancer, gastric, breast, pancreatic cancer, and oral squamous cell carcinoma patients (Cai et al 2006 J Clin Oncol.; Johnson JC et al 2006 Clin.Gastroentero Hepatol; Shrubroke MJ et al 2012 Can Prev Res.; Davenport JR et al 2016 Mol Carcinog). For example, it was shown that PGEM is significantly increased in patients with CRC compared to healthy individuals (Johnson JC et al 2006 Clin.Gastroentero Hepatol). [0015] Accordingly, in one aspect, the present invention provides a method of measuring a urinary concentration of PGEM in a patient, comprising measuring the concentration of PGEM in a urine sample of the patient using, for example, an LC–MS/MS method, such as any of the various LC–MS/MS methods described herein. In another aspect, the present invention provides a method of identifying or selecting a patient for treatment with an EP4 antagonist, comprising measuring the concentration of PGEM in a urine sample of the patient, for example, using an LC–MS/MS method as described herein, and selecting a patient having an elevated concentration of PGEM in a urine sample. In another aspect, the present invention provides a method of treating a proliferative disorder in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM, for example, using a method as described herein, and administering to the patient a therapeutically effective amount of an EP4 antagonist, for example, as described herein. In another aspect, the present invention provides a method of treating a proliferative disorder in a patient having an elevated urinary concentration of PGEM, for example, where the concentration of PGEM is determined using a method as described herein, and administering to the patient a therapeutically effective amount of an EP4 antagonist, such as any of the EP4 antagonists described herein. Also provided herein, in some aspects, are method, assays, and kits for detecting urinary PGEM concentrations. 2. Definitions [0016] As used herein, the term “an EP4 antagonist” refers to an agent that reduces or attenuates the signaling activity or biological activity of an EP4 receptor. Such agents can include proteins, such as anti-EP4 antibodies, nucleic acids, amino acids, peptides, carbohydrates, small molecules (organic or inorganic), or any other compound or composition which decreases the activity of an EP4 receptor, either by reducing the amount of EP4 receptor present in a cell, or by decreasing the binding or signaling activity or biological activity of the EP4 receptor. Various EP4 antagonists have been described previously, for example, in WO 2002/032900, WO 2005/021508, US 6,710,054, and US 7,238,714, the contents of which are incorporated herein by reference in their entireties, and others are described herein. [0017] As used herein, the terms “EP4 receptor activity” or “EP4 activity” refer to one or more changes in EP4 receptor-mediated downstream signaling activity or biological activity, such as, for example, an EP4-mediated increase in cAMP levels upon PGE2 stimulation, an EP4-mediated change in PI3K signaling, an EP4-mediated change in GSK3β signaling, an EP4-mediated change in one or more immune cell functions or inflammatory processes, such as modulating (e.g., decreasing or inhibiting) the activity of macrophages, neutrophils, cytotoxic lymphocytes, and/or NK cells, modulating (e.g., promoting or enhancing) the activity of tumor tolerant immune cells, such as myeloid derived suppressor cells and regulatory T cells, or any combination thereof of such EP4 receptor activities. [0018] As used herein, the term "antagonist" refers to a molecule that partially or fully blocks, inhibits, or neutralizes a biological activity of a native receptor or molecule disclosed herein (e.g., an EP4 receptor). In some embodiments, inhibition in the presence of the antagonist is observed in a dose-dependent manner. In some embodiments, the measured signal (e.g., signaling activity or biological activity) is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% lower than the signal measured with a negative control under comparable conditions. The potency of an antagonist is usually defined by its IC50 value (concentration required to inhibit 50% of the agonist response). The lower the IC50 value the greater the potency of the antagonist and the lower the concentration that is required to inhibit the maximum biological response. [0019] As used herein, the term “a selective EP4 antagonist” is an agent that inhibits EP4 activity with an IC50 at least 10-fold less, at least 20-fold less, at least 30-fold less, at least 40- fold less, at least 50-fold less, at least 60-fold less, at least 70-fold less, at least 80-fold less, at least 90-fold less, preferably, at least 100-fold less or more, than the IC50 for inhibition of EP1, EP2, or EP3 activity, as determined by standard methods known in the art. [0020] As used herein, the terms “measurable affinity” or “measurably inhibit” refers to a measurable change in EP4 activity between a sample comprising an EP4 antagonist described herein, or a salt or a composition thereof, and EP4, and an equivalent sample comprising EP4, in the absence of said compound, or composition thereof. As used herein, the term “LC-MS/MS,” “LC/MS/MS,” or “liquid chromatography tandem mass spectrometry” refers to an analytical technique that combines the separating power of liquid chromatography (LC) with the highly sensitive and selective mass analysis capability of triple quadrupole mass spectrometry based on the unique mass/charge (m/z) transitions of each compound of interest. Briefly, a sample solution containing analytes of interest is pumped through a stationary phase (LC column) by a mobile phase flowing through at high pressure. Chemical interaction between the components of the sample, the stationary phase, and the mobile phase affects different migration rates through the LC column affecting a separation. The wide variety of stationary phase and mobile phase combinations allow for customizing a separation to suit many complex solutions. After elution from the LC column, the effluent is directed to the mass spectrometer. The mass spectrometer for an LC/MS/MS system has an ionization source where the LC column effluent is nebulized, desolvated, and ionized creating charged particles. These charged particles then migrate under high vacuum through a series of mass analyzers (quadrupole) by applying electromagnetic fields. A specific mass/charge precursor ion (or parent ion) is targeted to pass through the first quadrupole, excluding all other mass/charge ratio particles. In the collision cell, the selected mass/charge ions are then fragmented into product ions (or daughter ions) by collision with an inert gas. The third quadrupole is used to target specific product ion fragments. The resulting isolated product ions are then quantified with an electron multiplier. This transition of ions from the precursor to product ion (also referred to as MS2) is highly specific to the structure of the compound of interest and therefore provides a high degree of selectivity. LC-MS/MS can be combined with other upstream processes such as solid phase extraction (SPE) and liquid phase extraction (LPE), as is known in the art, in some embodiments. Accordingly, as described herein, where a method of detecting the concentration of PGEM is said to use an “LC-MS/MS method,” that method can use any method known in the art involving LC-MS/MS. [0021] As used herein, the term “SPE-LC-MS/MS” or “solid phase extraction liquid chromatography tandem mass spectrometry” refers to a process or analytical technique in which a solid phase extraction (SPE) process is added upstream of the LC-MS/MS technique or method described above. SPE or solid phase extraction is a method of sample preparation that concentrates and purifies analytes from solution by sorption onto a disposable solid-phase cartridge, followed by elution of the analyte with a solvent appropriate for instrumental analysis. This is then followed by performing the LC-MS/MS method on the eluted analyte from the SPE process dissolved in the appropriate buffer. In some embodiments of the methods described herein, an “online SPE-LC- MS/MS” or “high-throughput SPE-LC-MS/MS” method can be used where a combined instrumentation setup allows for the SPE, LC, and MS steps to be performed without having to manually transfer the eluted analyte from the SPE to the LC-MS/MS instrument. Methods of performing SPE-LC-MS/MS and online SPE-LC-MS/MS are known in the art for detecting analytes like urinary PGEM and are described, for example, in Y Zhang, et al., J. Mass. Spectrom. 2011, 46, 705-711, the contents of which are incorporated herein by reference in their entirety. [0022] As used herein, “ELISA” or “enzyme-linked immunosorbent assay” is an immunoassay known in the art for detecting the presence of analytes in liquid samples, such as urine or serum samples. There are many types of ELISA methods, including, but not limited to, direct ELISAs, indirect ELISAs, sandwich ELISAs, competitive ELISAs, multiplex ELISAs, ELISPOT technologies, and other similar techniques known in the art. Principles of these immunoassay methods are known in the art, for example John R. Crowther, The ELISA Guidebook, 1st ed., Humana Press 2000, ISBN 0896037282, the contents of which are incorporated herein by reference in their entirety. Typically, ELISAs are performed with antibodies, but they can be performed with any capture agents that bind specifically to one or more biomarkers, such as PGEM, that can then be detected. Multiplex ELISA allows simultaneous detection of two or more analytes within a single compartment (e.g., microplate well) usually at a plurality of array addresses (Nielsen and Geierstanger 2004. J Immunol Methods 290: 107-20 (2004) and Ling et al.2007. Expert Rev Mol Diagn 7: 87-98 (2007)). [0023] As used herein, the terms "inhibits," “decreases,” “lowers,” or "reduces" are used interchangeably and encompass any measurable decrease in biological function and/or activity and/or concentration. For example, in some embodiments, an EP4 antagonist described herein inhibits or reduces EP4 function and/or activity in a given system or assay or subject by at least about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, or 100%, relative to a control or baseline amount of that function and/or activity. [0024] As used herein, the terms "increases," “elevates,” or “enhances,” are used interchangeably and encompass any measurable increase in a biological function and/or biological activity and/or a concentration. For example, an increase can be by at least about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, about 100%, about 2-fold, about 3-fold, about 4- fold, about 5-fold, about 6-fold, about 7-fold, about 8-fold, about 9-fold, about 10-fold, about 20- fold, about 25-fold, about 50-fold, about 100-fold, or higher, relative to a control or baseline amount of a function, or activity, or concentration. [0025] As used herein, the terms “elevated concentration,” “increased concentration,” “increased levels” of a substance (e.g., PGEM) in a sample refers to an increase in the amount of the substance of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, about 100%, about 2-fold, about 3-fold, about 4-fold, about 5-fold, about 6-fold, about 7-fold, about 8-fold, about 9-fold, about 10-fold, about 20-fold, about 25-fold, about 50-fold, about 100- fold, or higher, relative to the amount of the substance in a control sample or control samples, such as an individual or group of individuals who are not suffering from the disease or disorder (e.g., cancer) or an internal control, as determined by techniques known in the art. A subject can also be determined to have an “elevated concentration” of a substance if the concentration of the substance is increased by one standard deviation, two standard deviations, three standard deviations, four standard deviations, five standard deviations, or more relative to the mean (average) or median amount of the substance in a control group of samples or a baseline group of samples or a retrospective analysis of patient samples. As practiced in the art, such control or baseline levels can be previously determined, or measured prior to the measurement in the sample, or can be obtained from a database of such control samples. In other words, the control and subject samples do not have to be tested simultaneously. Similarly, “reduced concentration,” “decreased concentrations,” “lowered levels,” or “reduced levels” refers to a decrease in concentration or a decrease in level by at least about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, or 100% in a sample relative to a control. [0026] As used herein, a subject "in need of prevention," "in need of treatment," or "in need thereof," refers to one, who by the judgment of an appropriate medical practitioner (e.g., a doctor, a nurse, or a nurse practitioner in the case of humans; a veterinarian in the case of non-human mammals), would reasonably benefit from a given treatment or therapy. [0027] As used herein, the terms “treatment,” “treat,” and “treating” refer to preventing, reversing, alleviating, reducing the severity of, delaying the onset of, or inhibiting the progress of a disease or disorder, or one or more symptoms thereof, as described herein. In some embodiments, treatment can be administered after one or more symptoms have developed. In other embodiments, treatment can be administered in the absence of symptoms. For example, treatment can be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and/or in light of genetic or other susceptibility factors). Treatment can also be continued after symptoms have resolved, for example to prevent or delay their recurrence. [0028] As used herein, the terms “patient” or “subject” refer to an animal, preferably a mammal, and most preferably a human. [0029] As used herein, the term “a therapeutically effective amount of” refers to the amount of an EP4 antagonist (e.g., compound A, or a pharmaceutically acceptable salt thereof), which is effective to reduce or attenuate the biological activity of an EP4 receptor in a biological sample or in a patient. In some embodiments, “a therapeutically effective amount of” refers to the amount of an EP4 antagonist (e.g., compound A, or a pharmaceutically acceptable salt thereof), which measurably reduces the amount of EP4 receptor present in a cell. In some embodiments, “a therapeutically effective amount of” refers to the amount of an EP4 antagonist (e.g., compound A, or a pharmaceutically acceptable salt thereof), which measurably decreases the binding or signaling activity of the EP4 receptor or any EP4 receptor-mediated activity. [0030] As used herein, the term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1–19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2– hydroxy–ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2–naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3–phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p–toluenesulfonate, undecanoate, valerate salts, and the like. [0031] Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N ⁺ (C1–4alkyl)4 salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, loweralkyl sulfonate and aryl sulfonate. [0032] Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure; for example, the R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the invention. Unless otherwise stated, all tautomeric forms of the compounds of the invention are within the scope of the invention. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures including the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a ¹³ C- or ¹⁴ C-enriched carbon are within the scope of this invention. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents in accordance with the present invention. [0033] As used herein, the terms “about” or “approximately” have the meaning of within 20% of a given value or range. In some embodiments, the term “about” refers to within 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of a given value. 3. Description of Exemplary Methods and Uses [0034] In some aspects and embodiments, the present invention provides methods of identifying or selecting a patient having an elevated urinary concentration of PGEM for treatment with an EP4 antagonist, the methods comprising measuring the concentration of PGEM in a urine sample of the patient, for example, using an LC–MS/MS method as described herein, and selecting a patient having an elevated concentration of PGEM in the urine sample. In some embodiments, the method further comprises administering an EP4 antagonist to the patient having the elevated concentration of PGEM. [0035] In some embodiments, the present invention provides a method of measuring a urinary concentration of PGEM in a patient, comprising measuring the concentration of PGEM in a urine sample of the patient. In some embodiments, an LC-MS/MS method is used. In some embodiments, an LC–MS/MS method is an SPE-LC-MS/MS method, such as an online SPE-LC– MS/MS method. In some embodiments, the method of measuring the concentration of PGEM in the urine sample comprises an ELISA method. [0036] Methods of measuring or determining concentrations of analytes in biological samples, such as the urine, are known in the art and include, for example, mass spectrometry approaches, such as MS/MS, LC-MS/MS, multiple reaction monitoring (MRM) or SRM and product-ion monitoring (PIM), as well as antibody-based methods such as immunoassays, including Western blots, enzyme-linked immunosorbant assay (ELISA), immunoprecipitation, immunohistochemistry, immunofluorescence, radioimmunoassay, dot blotting, and flow cytometry-based methods. Accordingly, in some embodiments, determining the level or concentration of PGEM comprises using an immunoassay and/or mass spectrometric-based method. [0037] In some embodiments of the methods described herein, the method of measuring the concentration of PGEM in the urine sample comprises an LC-MS/MS method. Briefly, “LC- MS/MS,” or “liquid chromatography tandem mass spectrometry” is an analytical technique that combines liquid chromatography (LC) and triple quadrupole mass spectrometry (MS). Briefly, a sample solution containing analytes of interest, such as a urine sample or a processed urine sample from an SPE process, is pumped through a stationary phase (LC column) by a mobile phase flowing through at high pressure. After elution from the LC column, the effluent is directed to the mass spectrometer. The mass spectrometer for an LC-MS/MS system has an ionization source where the LC column effluent is nebulized, desolvated, and ionized creating charged particles. These charged particles then migrate or transition from a precursor ion under high vacuum through a series of mass analyzers (quadrupole) by applying electromagnetic fields, resulting in a product ion that is highly specific to the structure of the compound of interest and therefore provides a high degree of selectivity. [0038] In some embodiments, an SPE-LC-MS/MS method is used. SPE-LC-MS/MS or “solid phase extraction liquid chromatography tandem mass spectrometry” is a process or analytical technique in which a solid phase extraction (SPE) process is combined with the LC-MS/MS process. SPE is a method of sample preparation that concentrates and purifies analytes from solution by sorption onto a disposable solid-phase cartridge, followed by elution of the analyte with a solvent appropriate for subsequent instrumental analysis. In SPE-LC-MS/MS, the SPE process is then followed by performing the LC-MS/MS method on the eluted analyte from the SPE process, dissolved in the appropriate buffer. [0039] In some embodiments of the methods described herein, an “online SPE-LC-MS/MS” or “high-throughput SPE-LC-MS/MS” method is used where a combined instrumentation setup allows for the SPE, LC, and MS steps to be performed without having to manually transfer the eluted analyte from the SPE process to the LC-MS/MS instrument. Methods of performing SPE- LC-MS/MS and online SPE-LC-MS/MS are known in the art for detecting analytes like urinary PGEM and are described, for example, in Y Zhang, et al., J. Mass. Spectrom.2011, 46, 705-711, the contents of which are incorporated herein by reference in their entirety. [0040] In some embodiments, an LC–MS/MS method comprises a mobile phase at a pH of about 3.4-5.6. In some embodiments, an LC–MS/MS method comprises a mobile phase at a pH of about 3.4-4.0. In some embodiments, an LC–MS/MS method comprises a mobile phase at a pH of about 5.0-5.6. In some embodiments, an LC–MS/MS method comprises a mobile phase at a pH of about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, or about 5.0. In some embodiments, an LC–MS/MS method comprises a mobile phase at a pH of about 4.5. [0041] In some embodiments, an LC–MS/MS method comprises a mass spectrometer operating in MRM mode. In some embodiments, a sample is introduced into a mass spectrometer through electrospray ionization in negative ion mode. In some embodiments, a mass spectrometer has a source temperature at about 400 ^o C, about 450 ^o C, about 500 ^o C, about 550 ^o C, about 600 ^o C, about 650 ^o C, about 700 ^o C, about 750 ^o C, or about 800 ^o C. In some embodiments, a mass spectrometer has a source temperature at about 600 ^o C. In some embodiments, a mass spectrometer has an ionization energy at about -2500 V, -2600 V, -2700 V, -2800 V, -2900 V, -3000 V, -3100 V, -3200 V, -3300 V, -3400 V, -3500 V. In some embodiments, a mass spectrometer has an ionization energy at about -3000 V. In some embodiments, a mass spectrometer has a declustering potential of about -50 V, -55 V, -60 V, -65 V, -70 V, -75 V, -80 V, -85 V, or -90 V. In some embodiments, a mass spectrometer has a declustering potential of about -70 V. In some embodiments, a mass spectrometer has a collision energy of about -18 V, -20 V, -22 V, -24 V, -26 V, -28 V, or -30 V. In some embodiments, a mass spectrometer has a collision energy of about - 24 V. [0042] In some embodiments, the method of measuring the concentration of PGEM in the urine sample comprises an ELISA method. A non-limiting example of an ELISA method for use with the methods described herein includes a double antibody sandwich ELISA method using a monoclonal antibody specific against human PGEM that is detected using a labeled secondary antibody, such as a biotin-labeled secondary antibody, that can then be detected using an enzyme- conjugate, such as an avidin-peroxidase conjugate. A non-limiting example of such a PGEM ELISA that can be used with the methods described herein can be obtained from MyBioSource Cat. No. MBS773057. [0043] In some embodiments, a method of measuring a urinary concentration of PGEM in a patient comprises collecting a urine sample from a patient. In some embodiments, a urine sample is stored below room temperature until being analyzed. In some embodiments, a urine sample is stored at about 0 ^o C. In some embodiments, a urine sample is stored at about at about -10 ^o C, about -20 ^o C, about -30 ^o C, about -40 ^o C, about -50 ^o C, about -60 ^o C, about -70 ^o C, or about -80 ^o C until being analyzed. In some embodiments, a urine sample is frozen before being analyzed. In some embodiments, a urine sample is stored at about -80 ^o C before being analyzed. [0044] In some embodiments, a urine sample is diluted before being analyzed. In some embodiments, a urine sample is diluted in water. In some embodiments, a urine sample is diluted about 50-fold, about 100-fold, about 200-fold, about 300-fold, about 400-fold, about 500-fold, about 600-fold, about 700-fold, about 800-fold, about 900-fold, or about 1000-fold. In some embodiments, a urine sample is diluted less than 50-fold. In some embodiments, a urine sample is diluted about 1000-fold. In some embodiments, a urine sample is diluted more than 1000-fold. [0045] In some embodiments, a urine sample is spiked with an isotope-labeled creatinine as an internal standard. In some embodiments, a urine sample is diluted, for example with water as described herein, before being spiked with an isotope-labeled creatinine. Isotope-labeled creatinine differs from creatinine only in the presence of one or more isotopically enriched atoms. For example, isotope-labeled creatinine can be prepared by replacement of hydrogen by deuterium or tritium, and/or by replacement of a carbon by a ¹³ C- or ¹⁴ C-enriched carbon. In some embodiments, an isotope labeled creatinine is d3-deuterated creatinine. In some embodiments, an isotope-labeled creatinine is spiked at about 50, about 100, about 150, about 200, about 250, about 300, about 350, about 400, about 450, about 500, about 550, or about 600 ng/ml as an internal standard. In some embodiments, an isotope-labeled creatinine is spiked at about 400 ng/ml as internal standard. In some embodiments, an isotope-labeled creatinine is spiked at less than 50 ng/ml as an internal standard. In some embodiments, an isotope-labeled creatinine is spiked at more than 600 ng/ml as an internal standard. [0046] For use in the methods described herein, any screening assay for measuring the urinary concentration of PGEM normalizes the obtained PGEM level or concentration against the level or concentration of creatinine in the same urine sample. The level or concentration of a creatine in a given urine sample can be measured by a clinical urinary creatinine diagnostics test, such as those performed on Roche Modular or Cobas analyzers. [0047] Accordingly, as used herein the terms “elevated urinary concentration of PGEM,” “increased urinary concentration of PGEM,” “increased concentration of PGEM in a urine sample,” and “elevated concentration of PGEM in a urine sample,” refer to a concentration of PGEM normalized to the concentration of creatinine in a urine sample of a patient or subject, which is higher than the normal normalized concentration of PGEM in the urine, or equal to or higher than a selected or prespecified or predefined normalized concentration of PGEM in the urine. This higher value can be an increase in the amount of normalized PGEM of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, about 100%, about 1.5 fold, about 2-fold, about 3-fold, about 4-fold, about 5-fold, about 6-fold, about 7-fold, about 8-fold, about 9-fold, about 10-fold, about 20-fold, about 25-fold, about 50-fold, about 100-fold, or higher, relative to the amount of normalized PGEM in a control sample or control samples, such as an individual or group of individuals who are not suffering from the disease or disorder (e.g., cancer), or a control sample databased based on retrospective patient sample analysis, or an internal control, as determined by techniques known in the art. A urinary sample from a subject can also be determined or deemed to have an “elevated concentration of PGEM” if the normalized concentration of PGEM is increased by one standard deviation, two standard deviations, three standard deviations, four standard deviations, five standard deviations, or more, relative to the mean (average) or median amount of the substance in a control group of samples or a baseline group of samples. As practiced in the art, such control or baseline levels can be previously determined, or measured prior to the measurement in the sample, or can be obtained from a database of such control samples. The normal concentration of PGEM in the urine is about 10.6 ng/mg normalized to creatinine for males and about 6.0 ng/mg normalized to creatinine for females. [0048] Accordingly, in some embodiments of any of the aspects described herein, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 20% higher relative to the amount of normalized PGEM in a control sample or control samples. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 40% higher relative to the amount of normalized PGEM in a control sample or control samples. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 60% higher relative to the amount of normalized PGEM in a control sample or control samples. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 80% higher relative to the amount of normalized PGEM in a control sample or control samples. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 100% higher relative to the amount of normalized PGEM in a control sample or control samples. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 2-fold higher relative to the amount of normalized PGEM in a control sample or control samples. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 5-fold higher relative to the amount of normalized PGEM in a control sample or control samples. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 10-fold higher relative to the amount of normalized PGEM in a control sample or control samples. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 25-fold higher relative to the amount of normalized PGEM in a control sample or control samples. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 50-fold higher relative to the amount of normalized PGEM in a control sample or control samples. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized concentration of PGEM in a urine sample about 100-fold higher relative to the amount of normalized PGEM in a control sample or control samples. [0049] In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at more than about 10.6 ng/mg for a male patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at more than about 15, about 20, or about 25 ng/mg for a male patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at about 30 ng/mg or more for a male patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at about 35 ng/mg or more for a male patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at about 40 ng/mg or more for a male patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at about 45 ng/mg or more for a male patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at about 50 ng/mg or more for a male patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at more than about 55 ng/mg, about 60 ng/mg, 65 ng/mg, 70 ng/mg, or more for a male patient. [0050] In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at more than about 6.0 ng/mg for a female patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at more than about 9, about 12, or about 15 ng/mg for a female patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at about 18 ng/mg or more for a female patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at about 21 ng/mg or more for a female patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at about 24 ng/mg or more for a female patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at about 27 ng/mg or more for a female patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at about 30 ng/mg or more for a female patient. In some embodiments, an elevated concentration of PGEM in a urine sample refers to a normalized to creatine concentration of PGEM in a urine sample at more than about 33 ng/mg, about 36 ng/mg, about 39 ng/mg, 42 ng/mg, or more for a female patient. [0051] In some aspects and embodiments, a method of identifying or selecting a patient having an elevated urinary concentration of PGEM is for selecting a patient having a proliferative disorder. In some embodiments, the proliferative disorder is a cancer. In some embodiments, a cancer is selected from those as described herein. In some embodiments, an elevated concentration of PGEM in a urine sample of a patient having a proliferative disorder refers to a normalized to creatine concentration of PGEM in a urine sample at about 15 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a patient having a proliferative disorder refers to a normalized to creatine concentration of PGEM in a urine sample at about 30 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a patient having a proliferative disorder refers to a normalized to creatine concentration of PGEM in a urine sample at about 40 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a patient having a proliferative disorder refers to a normalized to creatine concentration of PGEM in a urine sample at about 50 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a patient having a proliferative disorder refers to a normalized to creatine concentration of PGEM in a urine sample at about 60 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a patient having a proliferative disorder refers to a normalized to creatine concentration of PGEM in a urine sample at about 70 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a patient having a proliferative disorder refers to a normalized to creatine concentration of PGEM in a urine sample at about 80 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a patient having a proliferative disorder refers to a normalized to creatine concentration of PGEM in a urine sample at about 90 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a patient having a proliferative disorder refers to a normalized to creatine concentration of PGEM in a urine sample at about 100 ng/mg or more. In some embodiments, a method of identifying or selecting a patient having an elevated urinary concentration of PGEM is for selecting a patient having colorectal cancer. In some embodiments, a method of identifying or selecting a patient having an elevated urinary concentration of PGEM is for selecting a patient having metastatic colorectal cancer. In some embodiments, a method of identifying or selecting a patient having an elevated urinary concentration of PGEM is for selecting a patient having microsatellite- stable (MSS) metastatic colorectal cancer. [0052] In some embodiments, an elevated concentration of PGEM in a urine sample of a colorectal cancer patient refers to a normalized to creatine concentration of PGEM in a urine sample at about 14.65 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a colorectal cancer patient refers to a normalized to creatine concentration of PGEM in a urine sample at about 20 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a colorectal cancer patient refers to a normalized to creatine concentration of PGEM in a urine sample at about 25 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a colorectal cancer patient refers to a normalized to creatine concentration of PGEM in a urine sample at about 30 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a colorectal cancer patient refers to a normalized to creatine concentration of PGEM in a urine sample at about 35 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a colorectal cancer patient refers to a normalized to creatine concentration of PGEM in a urine sample at about 40 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a colorectal cancer patient refers to a normalized to creatine concentration of PGEM in a urine sample at about 45 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a colorectal cancer patient refers to a normalized to creatine concentration of PGEM in a urine sample at about 50 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a colorectal cancer patient refers to a normalized to creatine concentration of PGEM in a urine sample at about 55 ng/mg or more. In some embodiments, an elevated concentration of PGEM in a urine sample of a colorectal cancer patient refers to a normalized to creatine concentration of PGEM in a urine sample at more than about 60 ng/ml, about 65 ng/ml, or about 70 ng/mg. [0053] In some aspects and embodiments, the present invention provides a method of treating a proliferative disorder in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, an elevated urinary concentration of PGEM is as described herein. [0054] In some embodiments, a proliferative disorder is a cancer as described herein. In some embodiments, a cancer is colorectal cancer (CRC). In some embodiments, a cancer is metastatic colorectal cancer. In some embodiments, a cancer is microsatellite-stable (MSS) metastatic colorectal cancer. In some embodiments, a cancer is advanced or progressive microsatellite-stable (MSS) CRC. In some embodiments, a cancer is non-small cell lung cancer (NSCLC). In some embodiments, a cancer is advanced and/or metastatic NSCLC. In some embodiments, a cancer is ovarian cancer. In some embodiments, a cancer is breast cancer. In some embodiments, a cancer is head and neck cancer. [0055] In some embodiments, the present invention provides a method of treating a cancer in a male patient, comprising selecting a patient having an elevated urinary concentration of PGEM at more than about 10 ng/ml, about 15 ng/ml, about 20 ng/ml, or about 25 ng/mg normalized to creatinine, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a male patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 30 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a male patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 35 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a male patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 40 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a male patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 45 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a male patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 50 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a male patient, comprising selecting a patient having an elevated urinary concentration of PGEM at more than about 55 ng/mg, about 60 ng/mg, about 65 ng/mg, or about 70 ng/mg normalized to creatinine, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. [0056] In some embodiments, the present invention provides a method of treating a cancer in a female patient, comprising selecting a patient having an elevated urinary concentration of PGEM at more than about 6 ng/mg, about 9 ng/mg, about 12 ng/mg, or 15 ng/mg normalized to creatinine, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a female patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 18 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a female patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 21 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a female patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 24 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a female patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 27 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a female patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 30 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the present invention provides a method of treating a cancer in a female patient, comprising selecting a patient having an elevated urinary concentration of PGEM at more than about 33 ng/mg, about 36 ng/mg, about 39 ng/mg, or about 42 ng/mg normalized to creatinine, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. [0057] In some aspects and embodiments, provided herein is a method of treating a proliferative disorder in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 15 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, the proliferative disorder is a cancer. In some embodiments, the cancer is selected from those as described herein. [0058] In some embodiments, a method of treating a proliferative disorder in a patient comprises selecting a patient having an elevated urinary concentration of PGEM at about 30 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, a method of treating a proliferative disorder in a patient comprises selecting a patient having an elevated urinary concentration of PGEM at about 40 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, a method of treating a proliferative disorder in a patient comprises selecting a patient having an elevated urinary concentration of PGEM at about 50 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, a method of treating a proliferative disorder in a patient comprises selecting a patient having an elevated urinary concentration of PGEM at about 60 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, a method of treating a proliferative disorder in a patient comprises selecting a patient having an elevated urinary concentration of PGEM at about 70 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, a method of treating a proliferative disorder in a patient comprises selecting a patient having an elevated urinary concentration of PGEM at about 80 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, a method of treating a proliferative disorder in a patient comprises selecting a patient having an elevated urinary concentration of PGEM at about 90 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some embodiments, a method of treating a proliferative disorder in a patient comprises selecting a patient having an elevated urinary concentration of PGEM at about 100 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. [0059] In some aspects and embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 15 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some aspects and embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 20 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some aspects embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 25 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some aspects and embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 30 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some aspects and embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 35 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some aspects and embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 40 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some aspects and embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 45 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. In some aspects and embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising selecting a patient having an elevated urinary concentration of PGEM at about 50 ng/mg normalized to creatinine or more, and administering to the patient a therapeutically effective amount of an EP4 antagonist, or a pharmaceutical composition thereof. [0060] In some embodiments, an EP4 antagonist is selected from those described in WO 2002/032900, WO 2005/021508, and US Patent Nos. 6,710,054 and 7,960,407, the contents of each of which are incorporated herein by reference in their entireties. [0061] In some aspects and embodiments, an EP4 antagonist is a compound of formula I: or a pharmaceutically acceptable salt thereof, wherein each variable is as described in WO 2002/032900, the contents of which is incorporated herein by reference in its entirety. [0062] In some embodiments, an EP4 antagonist is a compound of formula I’: or a pharmaceutically acceptable s iable is as described in WO 2005/021508, the contents of which is incorporated herein by reference in its entirety. [0063] In some embodiments, an EP4 antagonist is compound A: (also known as grapiprant), or a pharmaceutically a ccep a e sa ereo . n some em odiment, compound A is in crystal form. In some embodiments, compound A is in polymorph Form A, as described in US Patent Nos.7,960,407 and 9,265,756, the contents of which are incorporated herein by reference in their entireties. In some embodiments, polymorph Form A of compound A is characterized by a powder X-ray diffraction pattern obtained by irradiation with Cu Kα radiation which includes main peaks at 2- Theta° 9.8, 13.2, 13.4, 13.7, 14.1, 17.5, 19.0, 21.6, 24.0 and 25.7+/−0.2. In some embodiments, polymorph Form A of compound A is characterized by differential scanning calorimetry (DSC) in which it exhibits an endothermic event at about 160° C. In some embodiments, polymorph Form A of compound A exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 9.9, about 13.5, about 14.3, about 16.1, about 17.7, about 21.8, about 24.14, and about 25.8. In some embodiments, polymorph Form A of compound A exhibits a differential scanning calorimetry profile having showed an endotherm/exotherm at about 155-170° C. In some embodiments, polymorph Form A of compound A exhibits a thermogravimetric analysis showing a loss of mass of 0.5-0.6% when heated from about 30° to about 150° C. [0064] In some embodiments, the present invention provides a method of identifying or selecting a male patient having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC–MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 30 ng/mg or more. [0065] In some embodiments, the present invention provides a method of identifying or selecting a male patient having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC–MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 40 ng/mg or more. [0066] In some embodiments, the present invention provides a method of identifying or selecting a male patient having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC–MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 50 ng/mg or more. [0067] In some embodiments, the present invention provides a method of identifying or selecting a female patient having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC–MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 18 ng/mg or more. [0068] In some embodiments, the present invention provides a method of identifying or selecting a female patient having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC–MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 24 ng/mg or more. [0069] In some embodiments, the present invention provides a method of identifying or selecting a female patient having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC–MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 30 ng/mg or more. [0070] In some embodiments, the present invention provides a method of identifying or selecting a patient of a proliferative disorder having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 50 ng/mg or more. [0071] In some embodiments, the present invention provides a method of identifying or selecting a patient of a proliferative disorder having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 60 ng/mg or more. [0072] In some embodiments, the present invention provides a method of identifying or selecting a patient of a proliferative disorder having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 70 ng/mg or more. [0073] In some embodiments, the present invention provides a method of identifying or selecting a colorectal cancer patient having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 45 ng/mg or more. [0074] In some embodiments, the present invention provides a method of identifying or selecting a colorectal cancer patient having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 50 ng/mg or more. [0075] In some embodiments, the present invention provides a method of identifying or selecting a colorectal cancer patient having an elevated urinary concentration of PGEM, comprising measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein), and selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 60 ng/mg or more. [0076] In some embodiments, the present invention provides a method of treating a cancer in a male patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 30 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0077] In some embodiments, the present invention provides a method of treating a cancer in a male patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 40 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0078] In some embodiments, the present invention provides a method of treating a cancer in a male patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 50 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0079] In some embodiments, the present invention provides a method of treating a cancer in a female patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 18 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0080] In some embodiments, the present invention provides a method of treating a cancer in a female patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 24 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0081] In some embodiments, the present invention provides a method of treating a cancer in a female patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 30 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0082] In some embodiments, the present invention provides a method of treating a proliferative disorder in a patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 50 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0083] In some embodiments, the present invention provides a method of treating a proliferative disorder in a patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 60 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0084] In some embodiments, the present invention provides a method of treating a proliferative disorder in a patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 70 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0085] In some embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 45 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0086] In some embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 50 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0087] In some embodiments, the present invention provides a method of treating a colorectal cancer (e.g., MSS CRC) in a patient, comprising: measuring the concentration of PGEM in a urine sample of a patient using an LC– MS/MS method (for example, as described herein); selecting a patient having a normalized to creatinine concentration of PGEM in a urine sample at about 60 ng/mg or more; and administering to the patient a therapeutically effective amount of Compound A, or a pharmaceutically acceptable salt thereof. [0088] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered once daily. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered twice daily. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered three times daily. [0089] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered at a dosage of about 200-500 mg, about 250-450 mg, or about 300-450 mg per administration. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered at a dosage of about 200 or about 250 mg per administration. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered at a dosage of about 300 mg per administration. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered at a dosage of about 350 or about 400 mg per administration. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered at a dosage of about 450 or about 500 mg per administration. [0090] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered at a dosage of about 200-900 mg, about 250-900 mg, or about 300-900 mg per administration. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered at a dosage of about 600 or about 650 mg per administration. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered at a dosage of about 700 mg or 750 mg per administration. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered at a dosage of about 800 or about 850 mg per administration. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered at a dosage of about 900 mg per administration. [0091] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered twice a day, at a dosage of about 300 mg per administration. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered twice a day, at a dosage of about 450 mg per administration. [0092] In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered twice a day, at a dosage of about 600 mg per administration. In some embodiments, Compound A, or a pharmaceutically acceptable salt thereof, is administered twice a day, at a dosage of about 900 mg per administration. 4. Formulation and Administration [0093] In some embodiments, a method described herein comprises administering a pharmaceutical composition comprising an EP4 antagonist, as described herein, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. In some embodiments, the amount of an EP4 antagonist in a composition is such that is effective to measurably decrease the activity of an EP4 receptor in a biological sample or in a patient. In some embodiments, an EP4 antagonist composition is formulated for oral administration to a patient. [0094] The term “pharmaceutically acceptable carrier, adjuvant, or vehicle” refers to a non- toxic carrier, adjuvant, or vehicle that does not destroy the pharmacological activity of the compound with which it is formulated. Pharmaceutically acceptable carriers, adjuvants or vehicles that may be used in the compositions of this invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene- polyoxypropylene-block polymers, polyethylene glycol and wool fat. [0095] Compositions of the present invention may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir. The term "parenteral" as used herein includes subcutaneous, intravenous, intramuscular, intra-articular, intra-synovial, intrasternal, intrathecal, intrahepatic, intralesional and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intraperitoneally or intravenously. Sterile injectable forms of the compositions of this invention may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. [0096] For this purpose, any bland fixed oil may be employed including synthetic mono- or di-glycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as carboxymethyl cellulose or similar dispersing agents that are commonly used in the formulation of pharmaceutically acceptable dosage forms including emulsions and suspensions. Other commonly used surfactants, such as Tweens, Spans and other emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation. [0097] Pharmaceutically acceptable compositions of this invention may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, aqueous suspensions or solutions. In the case of tablets for oral use, carriers commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried cornstarch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring or coloring agents may also be added. [0098] Alternatively, pharmaceutically acceptable compositions of this invention may be administered in the form of suppositories for rectal administration. These can be prepared by mixing the agent with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature and therefore will melt in the rectum to release the drug. Such materials include cocoa butter, beeswax and polyethylene glycols. [0099] Pharmaceutically acceptable compositions of this invention may also be administered topically, especially when the target of treatment includes areas or organs readily accessible by topical application, including diseases of the eye, the skin, or the lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs. [00100] Topical application for the lower intestinal tract can be effected in a rectal suppository formulation (see above) or in a suitable enema formulation. Topically-transdermal patches may also be used. [00101] For topical applications, provided pharmaceutically acceptable compositions may be formulated in a suitable ointment containing the active component suspended or dissolved in one or more carriers. Carriers for topical administration of compounds of this invention include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax and water. Alternatively, provided pharmaceutically acceptable compositions can be formulated in a suitable lotion or cream containing the active components suspended or dissolved in one or more pharmaceutically acceptable carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water. [00102] For ophthalmic use, provided pharmaceutically acceptable compositions may be formulated as micronized suspensions in isotonic, pH adjusted sterile saline, or, preferably, as solutions in isotonic, pH adjusted sterile saline, either with or without a preservative such as benzylalkonium chloride. Alternatively, for ophthalmic uses, the pharmaceutically acceptable compositions may be formulated in an ointment such as petrolatum. [00103] Pharmaceutically acceptable compositions of this invention may also be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well- known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other conventional solubilizing or dispersing agents. [00104] Most preferably, pharmaceutically acceptable compositions of this invention are formulated for oral administration. Such formulations may be administered with or without food. In some embodiments, pharmaceutically acceptable compositions of this invention are administered without food. In other embodiments, pharmaceutically acceptable compositions of this invention are administered with food. [00105] The amount of compounds of the present invention that may be combined with the carrier materials to produce a composition in a single dosage form will vary depending upon the host treated, the particular mode of administration. Preferably, provided compositions should be formulated so that a dosage of between 0.01 - 100 mg/kg body weight/day of the antagonist can be administered to a patient receiving these compositions. [00106] It should also be understood that a specific dosage and treatment regimen for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, and the judgment of the treating physician and the severity of the particular disease being treated. The amount of a compound of the present invention in the composition will also depend upon the particular compound in the composition. 5. Uses [00107] In some embodiments, the present invention provides a method of treating a proliferative disorder in a patient comprising selecting a patient having an elevated urinary concentration of PGEM normalized to creatinine, for example, using a method as described herein, and administering to the patient a therapeutically effective amount of an EP4 antagonist, for example, as described herein. In some embodiments, a treatment method further comprises measuring the concentration of PGEM in a urine sample of a patient, for example, using an LC– MS/MS method as described herein. In some embodiments, a proliferative disorder is a cancer, for example, as described herein. [00108] In some embodiments, the present invention provides a method of treating a proliferative disorder in a patient having an elevated urinary concentration of PGEM normalized to creatinine, determined, for example, using a method as described herein, the method comprising administering to the patient having an elevated urinary concentration of PGEM normalized to creatinine a therapeutically effective amount of an EP4 antagonist, for example, as described herein. In some embodiments, a treatment method further comprises measuring the concentration of PGEM in a urine sample of a patient, for example, using an LC–MS/MS method as described herein. In some embodiments, a proliferative disorder is a cancer, for example, as described herein. Cancer [00109] The cancer or proliferative disorder or tumor to be treated using the methods and uses described herein include, but are not limited to, a hematological cancer, a lymphoma, a myeloma, a leukemia, a neurological cancer, skin cancer, breast cancer, a prostate cancer, a colorectal cancer, lung cancer, head and neck cancer, a gastrointestinal cancer, a liver cancer, a pancreatic cancer, a genitourinary cancer, a bone cancer, renal cancer, and a vascular cancer. [00110] A cancer to be treated using the methods described herein can be selected from colorectal cancer, such as microsatellite-stable (MSS) metastatic colorectal cancer, including advanced or progressive microsatellite-stable (MSS) CRC; non-small cell lung cancer (NSCLC), such as advanced and/or metastatic NSCLC; ovarian cancer; breast cancer, such as inflammatory breast cancer; endometrial cancer; cervical cancer; head and neck cancer; gastric cancer; gastroesophageal junction cancer; and bladder cancer. In some embodiments, a cancer is colorectal cancer. In some embodiments, the colorectal cancer is metastatic colorectal cancer. In some embodiments, the colorectal cancer is microsatellite-stable (MSS) metastatic colorectal cancer. In some embodiments, a cancer is advanced or progressive microsatellite-stable (MSS) CRC. In some embodiments, a cancer is non-small cell lung cancer (NSCLC). In some embodiments, a cancer is advanced and/or metastatic NSCLC. In some embodiments, a cancer is ovarian cancer. In some embodiments, a cancer is breast cancer. In some embodiments, a cancer is inflammatory breast cancer. In some embodiments, a cancer is endometrial cancer. In some embodiments, a cancer is endometrial cancer. In some embodiments, a cancer is head and neck cancer. In some embodiments, a cancer is gastric cancer. In some embodiments, a cancer is gastroesophageal junction cancer. In some embodiments, a cancer is bladder cancer. [00111] Cancer includes, in some embodiments, without limitation, leukemias (e.g., acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute myelomonocytic leukemia, acute monocytic leukemia, acute erythroleukemia, chronic leukemia, chronic myelocytic leukemia, chronic lymphocytic leukemia), polycythemia vera, lymphoma (e.g., Hodgkin’s disease or non-Hodgkin’s disease), Waldenstrom's macroglobulinemia, multiple myeloma, heavy chain disease, and solid tumors such as sarcomas and carcinomas (e.g., fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing’s tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilm's tumor, cervical cancer, uterine cancer, testicular cancer, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, glioblastoma multiforme (GBM, also known as glioblastoma), medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, schwannoma, neurofibrosarcoma, meningioma, melanoma, neuroblastoma, and retinoblastoma). [00112] In some embodiments, the cancer is glioma, astrocytoma, glioblastoma multiforme (GBM, also known as glioblastoma), medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, schwannoma, neurofibrosarcoma, meningioma, melanoma, neuroblastoma, or retinoblastoma. [00113] In some embodiments, the cancer is acoustic neuroma, astrocytoma (e.g. Grade I – Pilocytic Astrocytoma, Grade II – Low-grade Astrocytoma, Grade III – Anaplastic Astrocytoma, or Grade IV – Glioblastoma (GBM)), chordoma, CNS lymphoma, craniopharyngioma, brain stem glioma, ependymoma, mixed glioma, optic nerve glioma, subependymoma, medulloblastoma, meningioma, metastatic brain tumor, oligodendroglioma, pituitary tumors, primitive neuroectodermal (PNET) tumor, or schwannoma. In some embodiments, the cancer is a type found more commonly in children than adults, such as brain stem glioma, craniopharyngioma, ependymoma, juvenile pilocytic astrocytoma (JPA), medulloblastoma, optic nerve glioma, pineal tumor, primitive neuroectodermal tumors (PNET), or rhabdoid tumor. In some embodiments, the patient is an adult human. In some embodiments, the patient is a child or pediatric patient. [00114] Cancer includes, in another embodiment, without limitation, mesothelioma, hepatobilliary (hepatic and billiary duct), bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, ovarian cancer, colon cancer, rectal cancer, cancer of the anal region, stomach cancer, gastrointestinal (gastric, colorectal, and duodenal), uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin’s Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, prostate cancer, testicular cancer, chronic or acute leukemia, chronic myeloid leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, non-Hodgkins’s lymphoma, spinal axis tumors, brain stem glioma, pituitary adenoma, adrenocortical cancer, gall bladder cancer, multiple myeloma, cholangiocarcinoma, fibrosarcoma, neuroblastoma, retinoblastoma, or a combination of one or more of the foregoing cancers. [00115] In some embodiments, the cancer is selected from hepatocellular carcinoma, ovarian cancer, ovarian epithelial cancer, or fallopian tube cancer; papillary serous cystadenocarcinoma or uterine papillary serous carcinoma (UPSC); prostate cancer; testicular cancer; gallbladder cancer; hepatocholangiocarcinoma; soft tissue and bone synovial sarcoma; rhabdomyosarcoma; osteosarcoma; chondrosarcoma; Ewing sarcoma; anaplastic thyroid cancer; adrenocortical adenoma; pancreatic cancer; pancreatic ductal carcinoma or pancreatic adenocarcinoma; gastrointestinal/stomach (GIST) cancer; lymphoma; squamous cell carcinoma of the head and neck (SCCHN); salivary gland cancer; glioma, or brain cancer; neurofibromatosis-1 associated malignant peripheral nerve sheath tumors (MPNST); Waldenstrom’s macroglobulinemia; or medulloblastoma. [00116] In some embodiments, the cancer is selected from hepatocellular carcinoma (HCC), hepatoblastoma, colon cancer, rectal cancer, ovarian cancer, ovarian epithelial cancer, fallopian tube cancer, papillary serous cystadenocarcinoma, uterine papillary serous carcinoma (UPSC), hepatocholangiocarcinoma, soft tissue and bone synovial sarcoma, rhabdomyosarcoma, osteosarcoma, anaplastic thyroid cancer, adrenocortical adenoma, pancreatic cancer, pancreatic ductal carcinoma, pancreatic adenocarcinoma, glioma, neurofibromatosis-1 associated malignant peripheral nerve sheath tumors (MPNST), Waldenstrom’s macroglobulinemia, or medulloblastoma. [00117] In some embodiments, the cancer is a solid tumor, such as a sarcoma, carcinoma, or lymphoma. Solid tumors generally comprise an abnormal mass of tissue that typically does not include cysts or liquid areas. In some embodiments, the cancer is selected from renal cell carcinoma, or kidney cancer; hepatocellular carcinoma (HCC) or hepatoblastoma, or liver cancer; melanoma; breast cancer; colorectal carcinoma, or colorectal cancer; colon cancer; rectal cancer; anal cancer; lung cancer, such as non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC); ovarian cancer, ovarian epithelial cancer, ovarian carcinoma, or fallopian tube cancer; papillary serous cystadenocarcinoma or uterine papillary serous carcinoma (UPSC); prostate cancer; testicular cancer; gallbladder cancer; hepatocholangiocarcinoma; soft tissue and bone synovial sarcoma; rhabdomyosarcoma; osteosarcoma; chondrosarcoma; Ewing sarcoma; anaplastic thyroid cancer; adrenocortical carcinoma; pancreatic cancer; pancreatic ductal carcinoma or pancreatic adenocarcinoma; gastrointestinal/stomach (GIST) cancer; lymphoma; squamous cell carcinoma of the head and neck (SCCHN); salivary gland cancer; glioma, or brain cancer; neurofibromatosis-1 associated malignant peripheral nerve sheath tumors (MPNST); Waldenstrom’s macroglobulinemia; or medulloblastoma. [00118] In some embodiments, the cancer is selected from renal cell carcinoma, hepatocellular carcinoma (HCC), hepatoblastoma, colorectal carcinoma, colorectal cancer, colon cancer, rectal cancer, anal cancer, ovarian cancer, ovarian epithelial cancer, ovarian carcinoma, fallopian tube cancer, papillary serous cystadenocarcinoma, uterine papillary serous carcinoma (UPSC), hepatocholangiocarcinoma, soft tissue and bone synovial sarcoma, rhabdomyosarcoma, osteosarcoma, chondrosarcoma, anaplastic thyroid cancer, adrenocortical carcinoma, pancreatic cancer, pancreatic ductal carcinoma, pancreatic adenocarcinoma, glioma, brain cancer, neurofibromatosis-1 associated malignant peripheral nerve sheath tumors (MPNST), Waldenstrom’s macroglobulinemia, or medulloblastoma. [00119] In some embodiments, the cancer is selected from hepatocellular carcinoma (HCC), hepatoblastoma, colon cancer, rectal cancer, ovarian cancer, ovarian epithelial cancer, ovarian carcinoma, fallopian tube cancer, papillary serous cystadenocarcinoma, uterine papillary serous carcinoma (UPSC), hepatocholangiocarcinoma, soft tissue and bone synovial sarcoma, rhabdomyosarcoma, osteosarcoma, anaplastic thyroid cancer, adrenocortical carcinoma, pancreatic cancer, pancreatic ductal carcinoma, pancreatic adenocarcinoma, glioma, neurofibromatosis-1 associated malignant peripheral nerve sheath tumors (MPNST), Waldenstrom’s macroglobulinemia, or medulloblastoma. [00120] In some embodiments, the cancer is hepatocellular carcinoma (HCC). In some embodiments, the cancer is hepatoblastoma. In some embodiments, the cancer is colon cancer. In some embodiments, the cancer is rectal cancer. In some embodiments, the cancer is ovarian cancer, or ovarian carcinoma. In some embodiments, the cancer is ovarian epithelial cancer. In some embodiments, the cancer is fallopian tube cancer. In some embodiments, the cancer is papillary serous cystadenocarcinoma. In some embodiments, the cancer is uterine papillary serous carcinoma (UPSC). In some embodiments, the cancer is hepatocholangiocarcinoma. In some embodiments, the cancer is soft tissue and bone synovial sarcoma. In some embodiments, the cancer is rhabdomyosarcoma. In some embodiments, the cancer is osteosarcoma. In some embodiments, the cancer is anaplastic thyroid cancer. In some embodiments, the cancer is adrenocortical carcinoma. In some embodiments, the cancer is pancreatic cancer, or pancreatic ductal carcinoma. In some embodiments, the cancer is pancreatic adenocarcinoma. In some embodiments, the cancer is glioma. In some embodiments, the cancer is malignant peripheral nerve sheath tumors (MPNST). In some embodiments, the cancer is neurofibromatosis-1 associated MPNST. In some embodiments, the cancer is Waldenstrom’s macroglobulinemia. In some embodiments, the cancer is medulloblastoma. [00121] In some embodiments, the cancer is Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Adrenocortical Carcinoma, Anal Cancer, Appendix Cancer, Atypical Teratoid/Rhabdoid Tumor, Basal Cell Carcinoma, Bile Duct Cancer, Bladder Cancer, Bone Cancer, Brain Tumor, Astrocytoma, Brain and Spinal Cord Tumor, Brain Stem Glioma, Central Nervous System Atypical Teratoid/Rhabdoid Tumor, Central Nervous System Embryonal Tumors, Breast Cancer, Bronchial Tumors, Burkitt Lymphoma, Carcinoid Tumor, Carcinoma of Unknown Primary, Central Nervous System Cancer, Cervical Cancer, Childhood Cancers, Chordoma, Chronic Lymphocytic Leukemia (CLL), Chronic Myelogenous Leukemia (CML), Chronic Myeloproliferative Disorders, Colon Cancer, Colorectal Cancer, Craniopharyngioma, Cutaneous T-Cell Lymphoma, Ductal Carcinoma In Situ (DCIS), Embryonal Tumors, Endometrial Cancer, Ependymoblastoma, Ependymoma, Esophageal Cancer, Esthesioneuroblastoma, Ewing Sarcoma, Extracranial Germ Cell Tumor, Extragonadal Germ Cell Tumor, Extrahepatic Bile Duct Cancer, Eye Cancer, Fibrous Histiocytoma of Bone, Gallbladder Cancer, Gastric Cancer, Gastrointestinal Carcinoid Tumor, Gastrointestinal Stromal Tumors (GIST), Germ Cell Tumor, Ovarian Germ Cell Tumor, Gestational Trophoblastic Tumor, Glioma, Hairy Cell Leukemia, Head and Neck Cancer, Heart Cancer, Hepatocellular Cancer, Histiocytosis, Langerhans Cell Cancer, Hodgkin Lymphoma, Hypopharyngeal Cancer, Intraocular Melanoma, Islet Cell Tumors, Kaposi Sarcoma, Kidney Cancer, Langerhans Cell Histiocytosis, Laryngeal Cancer, Leukemia, Lip and Oral Cavity Cancer, Liver Cancer, Lobular Carcinoma In Situ (LCIS), Lung Cancer, Lymphoma, AIDS-Related Lymphoma, Macroglobulinemia, Male Breast Cancer, Medulloblastoma, Medulloepithelioma, Melanoma, Merkel Cell Carcinoma, Malignant Mesothelioma, Metastatic Squamous Neck Cancer with Occult Primary, Midline Tract Carcinoma Involving NUT Gene, Mouth Cancer, Multiple Endocrine Neoplasia Syndrome, Multiple Myeloma/Plasma Cell Neoplasm, Mycosis Fungoides, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasm, Chronic Myelogenous Leukemia (CML), Acute Myeloid Leukemia (AML), Myeloma, Multiple Myeloma, Chronic Myeloproliferative Disorder, Nasal Cavity Cancer, Paranasal Sinus Cancer, Nasopharyngeal Cancer, Neuroblastoma, Non- Hodgkin Lymphoma, Non-Small Cell Lung Cancer, Oral Cancer, Oral Cavity Cancer, Lip Cancer, Oropharyngeal Cancer, Osteosarcoma, Ovarian Cancer, Pancreatic Cancer, Papillomatosis, Paraganglioma, Paranasal Sinus Cancer, Nasal Cavity Cancer, Parathyroid Cancer, Penile Cancer, Pharyngeal Cancer, Pheochromocytoma, Pineal Parenchymal Tumors of Intermediate Differentiation, Pineoblastoma, Pituitary Tumor, Plasma Cell Neoplasm, Pleuropulmonary Blastoma, Breast Cancer, Primary Central Nervous System (CNS) Lymphoma, Prostate Cancer, Rectal Cancer, Renal Cell Cancer, Clear cell renal cell carcinoma, Renal Pelvis Cancer, Ureter Cancer, Transitional Cell Cancer, Retinoblastoma, Rhabdomyosarcoma, Salivary Gland Cancer, Sarcoma, Sezary Syndrome, Skin Cancer, Small Cell Lung Cancer, Small Intestine Cancer, Soft Tissue Sarcoma, Squamous Cell Carcinoma, Squamous Neck Cancer with Occult Primary, Squamous Cell Carcinoma of the Head and Neck (HNSCC), Stomach Cancer, Supratentorial Primitive Neuroectodermal Tumors, T-Cell Lymphoma, Testicular Cancer, Throat Cancer, Thymoma, Thymic Carcinoma, Thyroid Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Triple Negative Breast Cancer (TNBC), Gestational Trophoblastic Tumor, Unknown Primary, Unusual Cancer of Childhood, Urethral Cancer, Uterine Cancer, Uterine Sarcoma, Waldenstrom Macroglobulinemia, or Wilms Tumor. [00122] In certain embodiments, the cancer is selected from bladder cancer, breast cancer (including TNBC), cervical cancer, colorectal cancer, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), esophageal adenocarcinoma, glioblastoma, head and neck cancer, leukemia (acute and chronic), low-grade glioma, lung cancer (including adenocarcinoma, non-small cell lung cancer, and squamous cell carcinoma), Hodgkin's lymphoma, non-Hodgkin lymphoma (NHL), melanoma, multiple myeloma (MM), ovarian cancer, pancreatic cancer, prostate cancer, renal cancer (including renal clear cell carcinoma and kidney papillary cell carcinoma), and stomach cancer. [00123] In some embodiments, the cancer is small cell lung cancer, non-small cell lung cancer, colorectal cancer, multiple myeloma, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), pancreatic cancer, liver cancer, hepatocellular cancer, neuroblastoma, other solid tumors or other hematological cancers. [00124] In some embodiments, the cancer is small cell lung cancer, non-small cell lung cancer, colorectal cancer, multiple myeloma, or AML. [00125] The present invention further features methods and compositions for the diagnosis, prognosis and treatment of viral-associated cancers, including human immunodeficiency virus (HIV) associated solid tumors, human papilloma virus (HPV)-16 positive incurable solid tumors, and adult T-cell leukemia, which is caused by human T-cell leukemia virus type I (HTLV-I) and is a highly aggressive form of CD4+ T-cell leukemia characterized by clonal integration of HTLV- I in leukemic cells (See https://clinicaltrials.gov/ct2/show/study/ NCT02631746); as well as virus- associated tumors in gastric cancer, nasopharyngeal carcinoma, cervical cancer, vaginal cancer, vulvar cancer, squamous cell carcinoma of the head and neck, and Merkel cell carcinoma. (See https://clinicaltrials.gov/ct2/show/study/NCT02488759; see also https://clinicaltrials.gov/ct2/show/study/NCT0240886; https://clinicaltrials.gov/ct2/show/ NCT02426892) [00126] In some embodiments, the present invention provides a method for treating a cancer or a tumor in a patient in need thereof, comprising administering to the patient an agent that inhibits prostaglandin EP4 receptor (EP4) activity and an immuno-oncology agent as described herein, or pharmaceutical compositions thereof described herein. In some embodiments, the cancer or tumor comprises any of the cancers described herein. In some embodiments, the cancer comprises melanoma cancer. In some embodiments, the cancer comprises breast cancer. In some embodiments, the cancer comprises lung cancer. In some embodiments the cancer comprises small cell lung cancer (SCLC). In some embodiments, the cancer comprises non-small cell lung cancer (NSCLC). [00127] In some embodiments, the methods or uses described herein inhibit or reduce or arrest the growth or spread of a cancer or tumor. In some embodiments, the methods or uses described herein inhibit or reduce or arrest further growth of the cancer or tumor. In some embodiments, the methods or uses described herein reduce the size (e.g., volume or mass) of the cancer or tumor by at least 5%, at least 10%, at least 25%, at least 50%, at least 75%, at least 90% or at least 99% relative to the size of the cancer or tumor prior to treatment. In some embodiments, the methods or uses described herein reduce the quantity of the cancers or tumors in the patient by at least 5%, at least 10%, at least 25%, at least 50%, at least 75%, at least 90% or at least 99% relative to the quantity of cancers or tumors prior to treatment. [00128] The compounds and compositions, according to the methods of the present invention, can be administered using any amount and any route of administration effective for treating or lessening the severity of a cancer or tumor. The exact amount required varies from subject to subject, depending on the species, age, and general condition of the subject, the severity of the disease or condition, the particular agent, its mode of administration, and the like. The compounds and compositions, according to the methods of the present invention, are preferably formulated in dosage unit form for ease of administration and uniformity of dosage. The expression “dosage unit form” as used herein refers to a physically discrete unit of agent appropriate for the patient to be treated. It will be understood, however, that the total daily usage of the compounds and compositions is decided by the attending physician within the scope of sound medical judgment. The specific effective dose level for any particular patient or organism depends upon a variety of factors, including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed, and like factors well known in the medical arts. The terms “patient” or “subject,” as used herein, means an animal, preferably a mammal, and most preferably a human. [00129] Pharmaceutically acceptable compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), bucally, as an oral or nasal spray, or the like, depending on the severity of the disease or disorder being treated. In certain embodiments, the compounds of the invention can be administered orally or parenterally at dosage levels of about 0.01 mg/kg to about 50 mg/kg and preferably from about 1 mg/kg to about 25 mg/kg, of subject body weight per day, one or more times a day, to obtain the desired therapeutic effect. [00130] Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. [00131] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer’s solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. [00132] Injectable formulations can be sterilized, for example, by filtration through a bacterial- retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. [00133] In order to prolong the effect of a compound as described herein, it is often desirable to slow the absorption of the compound from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the compound then depends upon its rate of dissolution that, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered compound form is accomplished by dissolving or suspending the compound in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the compound in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of compound to polymer and the nature of the particular polymer employed, the rate of compound release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the compound in liposomes or microemulsions that are compatible with body tissues. [00134] Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. [00135] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. [00136] Solid compositions of a similar type can also be employed as fillers in soft and hard- filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They can optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polethylene glycols and the like. [00137] The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. [00138] Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, and eye drops are also contemplated as being within the scope of this invention. Additionally, the present invention contemplates the use of transdermal patches, which have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel. EXEMPLIFICATION [00139] The following examples are provided for illustrative purposes only and are not to be construed as limiting this invention in any manner. [00140] An EP4 antagonist described herein can be synthesized using the methods described in WO 2002/032900, WO 2005/021508, and US patent Nos.6,710,054 and 7,960,407, the contents of each of which are incorporated herein by reference in their entireties. Exemplary protocols for preparing polymorph form A of compound A are described in US Patent Nos. 7,960,407 and 9,265,756, the contents of each of which are incorporated herein by reference in their entireties. [00141] Abbreviations: PG: prostaglandin COX: cyclooxygenase HPLC: high-performance liquid chromatography MS: mass spectrometry PGEM or PGE-M: 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid GC: gas chromatography LC: liquid chromatography NMR: nuclear magnetic resonance ESI: electrospray ionization SRM: selected reaction monitoring CID: collision-induced dissociation; Cr: creatinine; ANOVA: analysis of variance BID: twice a day Example 1. Quantification of PGE-M using a liquid chromatography (LC)/tandem MS (LC/MS/MS) assay [00142] A description of this method can be found in LJ Murphey, et al., Analytical Biochemistry 334 (2004) 266–275, the content of which is incorporated herein by reference in its entirety. Reagents [00143] Methoxyamine HCl and [ ³ H ₇ ]PGE ₂ were obtained from commercial vendors. All organic reagents were of HPLC quality. Preparation of PGE-M standards [00144] Synthesis of PGE-M, the major urinary metabolite of PGE2 in humans, was performed according to the method as described in DF Taber, et al., J. Org. Chem. 67 (2002) 1607-1612. Structural identity of the compound was confirmed by MS and nuclear magnetic resonance (NMR). Subsequently, PGE-M was converted to the O-methyloxime derivative by treatment with methoxyamine HCl [JD Morrow, et al., Anal. Biochem.193 (1991) 142-148]. To prepare the assay internal standard, chemically synthesized PGE-M was converted to a [ ² H ₆ ]O-methyloxime derivative by treatment with [ ² H ₃ ]O-methoxyamine HCl. The deuterated internal standard has an unlabeled blank of 2 parts per 1000 when analyzed by LC/electrospray ionization (ESI) MS. The molecular ions ([M-H]- ) of the unlabeled ( ² H0) and ² H6-labeled O-methyloxime PGE-M standards are m/z 385 and 391, respectively. Sample preparation [00145] Urine (1 ml) was acidified to pH 3 with 1 M HCl, and endogenous PGE-M was then converted to the O-methyloxime derivative by treatment with 0.5 ml of 16% (w/v) methyloxime HCl in 1.5 M sodium acetate buffer (pH 5). Following a 1-h incubation, the methoximated PGE- M was extracted with 10 ml water adjusted to pH 3, and the aqueous sample was applied to a C- 18 Sep-Pak (Waters, Milford, MA, USA) that had been preconditioned with 5 ml methanol and 5 ml water (pH 3). The Sep-Pak was washed with 20 ml water (pH 3) and 10 ml heptane. PGE-M was then eluted from the Sep-Pak with 5 ml ethyl acetate, and any residual aqueous material was removed from the eluate by aspiration. The [ ² H6]O-methyloxime PGE-M internal standard (6.2 ng in 10 µl ethanol) was then added, and the eluate was evaporated under a continuous stream of nitrogen at 37 °C. The dried residue was resuspended in 50 µl mobile phase A (see below) and was filtered through a 0.2-micron Spin-X filter (Corning, Corning, NY, USA). [00146] Below is a scheme for the purification, derivatization, and analysis of PGE-M: Sample analysis by LC/MS/MS [00147] LC was performed on a 2.1x 50-mm, 5-_m particle Zorbax Eclipse XDB-C18 column (Aligent, Palo Alto, CA, USA) attached to a Surveyor MS Pump (Thermo-Finnigan, San Jose, CA, USA). Mobile phase A was 95:4.9:0.1 (v/v/v) 5 mM ammonium acetate:acetonitrile:acetic acid, and mobile phase B was 10.0:89.9:0.1 (v/v/v) 5 mM ammonium acetate:acetonitrile:acetic acid. Samples were separated by a gradient of 98–40% of mobile phase A over 15 min at a flow rate of 75µl/min prior to delivery to a ThermoFinnigan TSQ Quantum triple quadrupole mass spectrometer operating in the selected reaction monitoring (SRM) mode. The ESI source used nitrogen for both sheath and auxiliary gas set at 60 psi and 7 L/min, respectively. The mass spectrometer was operated in the negative ion mode with a capillary temperature of 210 °C, a spray voltage of 3.0kV, and a tube lens voltage of 118 V. The source collision-induced dissociation (CID) was set at 10eV. Precursor ions (m/z 385 and 391 for unlabeled PGE-M and the [ ² H6]PGE- M internal standard, respectively) were collisionally activated at 22 eV under 1.5 mT argon gas. For endogenous PGE-M, the predominant product ion m/z 336 representing [M - (OCH ₃ + H ₂ O)]- and the analogous ion, m/z 339 [M - (OC[ ² H3]+H2O)]- , for the deuterated internal standard were monitored in SRM mode. Quantification of endogenous PGE-M used the ratio of the mass chromatogram peak areas of the m/z 336 and 339 ions. Urinary 2,3-dinor-6-keto-PGF _1α was determined as described previously [VC Daniel, et al., J. Chromatogr. B 653 (1994) 117–122]. Data are expressed after correction for urinary creatinine (Cr) concentrations and are reported as nanograms per milligram Cr. Urine Cr was measured by an Autoanalyzer technique (Technicon, BuValo Grove, IL, USA). Human studies [00148] Two studies were conducted involving patients with colorectal cancer (CRC). Compound A was administered at doses of 300 BID or 450 BID. The baseline, i.e., prior to treatment with Compound A, urinary concentrations of PGE-M of study #1 are shown in Table 1 and FIG.1 A and 1B. The urinary concentrations of PGE-M of study #2 are shown in Table 2 and FIG.2. Table 1. Baseline urinary concentrations of PGE-M in CRC patients. Table 2. Baseline urinary concentrations of PGE-M in NSCLC patients. Patient # Dose Sex PGE-M (ng/mg Cr) Example 2. Quantification of PGE-M using a high-throughput online SPE-LC–MS/MS assay [00149] A description of this method can be found in Y Zhang, et al., J. Mass. Spectrom.2011, 46, 705-711, the content of which is incorporated herein by reference in its entirety. Chemicals and reagents [00150] tPGDM (9α-hydroxy-11,15-dioxo-2,3,4,5-tetranor-prostan-1,20-dioic acid), tPGDM- d6 (9α-hydroxy-11,15-dioxo-2,3,4,5-tetranorprostan-1,20-dioic acid-17,17,18,18,19,19-d6), tPGEM (11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostan-1,20-dioic acid), tPGEM-d6 (11α- hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostan-1,20-dioic acid-17,17,18,18,19,19-d6), methoxyamine hydrochloride, creatinine, creatinine-d3, acetonitrile, ammonium hydroxide, and ethyl acetate were obtained from commercial vendors. All mobile phase solvents were HPLC grade, and all reagents were analytical reagent grade. Collection and storage of human urine [00151] Random spot urine samples were collected from patients. Urine was collected in a polystyrene bottle, aliquoted and frozen at −80◦ C until analysis. Creatinine analysis [00152] Creatinine concentrations were measured by LC–MS/MS as previously described [JR Neale, et al., J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2008, 871, 72] with slight modification: Chromatographic separation was performed on a Kinetex 2.6 µm 50 mm × 3 mm C18 column using 0.1% formic acid as mobile phase A and acetonitrile as mobile phase B with 5.00 µl of the sample injection volume. Chromatographic elution was performed using a gradient of 0–2.00% mobile phase B for the first 2 min followed by 0.6 min at 50% B at a flow rate of 0.300 ml/min. Detection was performed using an API 4000 Mass Spectrometer operating in multiple reaction monitoring (MRM) mode. Urine samples were diluted 1000-fold in water and spiked with a d3-deuterated creatinine at 400 ng/ml as internal standard (IS). Preparation of calibration standards and quality control (QC) samples [00153] The main stock solution of analyte was prepared at 1.0 mg/ml in ethyl acetate and stored at −80 ^o C in a glass vessel. The calibration standards were prepared by adding appropriate amounts of the stock solution or subsequent calibration standards to blank artificial urine. Artificial urine contains the following components: 24.2 g/l of urea, 10.0 g/l of sodium chloride, 6.0 g/l of potassium chloride, 6.4 g/l of sodium dibasic phosphate, 2.0 g/l of creatinine and 50 mg/l of albumin (pH 7.5 adjusted using 1M hydrochloric acid). Nominal concentrations of calibration standards for tPGDM/tPGEM were 0.200/0.500, 0.400/1.00, 1.00/2.50, 2.00/5.00, 6.00/15.0, 10.0/25.0, 20.0/50.0 and 40.0/100 ng/ml in artificial urine. QC samples were prepared at three concentration levels using pooled human urine. Low-QC (LQC) contained only endogenous baseline levels of tPGDM/tPGEM, while both mid-QC (MQC) and high-QC (HQC) contained endogenous and spiked analytes. Derivatization of analytes and ISs in biological samples, calibrator standards and QC samples [00154] Derivatization of analytes/ISs using methoxyamine was performed based on a previously published method [WL Song, et al., J. Biol. Chem.2008, 283, 1179]. Briefly, 500 µl of samples was mixed with 25 µl methoxyamine (1.0 g/ml in water) and 25 µl of IS solution (100 ng/ml of tPGDM-d6 and tPGEM-d6). Samples were then incubated at room temperature for 30 min. Finally, 100 µl of the above samples was injected to online SPE-LC–MS/MS system as described below. Online SPE-LC–MS/MS [00155] Sample analysis was performed using a API 4000 Mass Spectrometer (SCIEX) equipped with an Agilent 1100 HPLC for online SPE/sample trapping, a Shimadzu HPLC LC-20 AD for sample analysis and a CTC PAL autosampler. Mobile phase A was HPLC-grade water containing 0.1% (v/v) acetic acid (around pH 4.5). Mobile phase B was HPLC grade methanol. Online SPE was performed on a Betasil C1 column (5 µm, 10 mm × 2.1 mm) using 20% mobile phase B for 2 min with a flow rate of 1.0 ml/min to trap and purify analytes. [00156] Chromatographic separation of derivatized tPGDM and tPGEM was performed by back flushing the trapped analytes into a Kinetex C18 analytical column (2.6 µm, 50 mm × 3 mm) using a gradient of 40–50% mobile phase B for 4 min with a flow rate of 0.5 ml/min. Detection was performed by an API 4000 Mass Spectrometer operating in MRM mode. Samples were introduced into the mass spectrometer through electrospray ionization in negative ion mode. The source temperature was 600◦ C. The ionization energy was set at −3000 V. The transitions monitored for modified tPGDM or tPGEM and the modified IS were m/z 385.2 → 336.2 and 391.2 → 342.2, respectively, with a declustering potential of −70 V and a collision energy of −24 V. The dwell time for each transition was 100 ms. MRM data were acquired by Analyst 1.4.2 software. The calibration curves were constructed based on the response ratio of peak area between analytes and their internal standards versus nominal standard concentrations by least-squares linear regression using a weighting factor of 1/x ² . Concentrations of QC samples or unknown samples were determined using the response ratio from QC samples or unknown samples and the linear regression curve. Example 3. Determination and Quantification of Tetranor-PGEM in Human Urine Using Liquid Chromatography with Tandem Mass Spectrometric Detection BRIEF METHOD SUMMARY Extraction Type Supported-liquid extraction Pre-screen Blank Matrix Surrogate matrix used for CALs and blanks. Urine M et o pec c equ rements [00157] Calibration Curve Set Up. Duplicate calibration curves. [00158] Surrogate Matrix. Due to the endogenous levels of the analyte of interest in urine, an analyte free surrogate matrix is used for certain functions. The surrogate matrix, SURINE ^TM Negative urine control (Synthetic urine), will be used for the preparation of the calibration curve, as a diluent for any samples require dilution, and as matrix blanks. Pre-Screen Blank Matrix. Prior to spiking any QCs (quality controls) that contain a urine component, the urine is analyzed two different days and the average of two days is taken to determine the endogenous Tetranor-PGEM concentration. Endogenous concentration is determined by analyzing n≥6, extracted with ISTD in a batch containing calibration curves and batch acceptance QCs. Batch acceptance QCs can be surrogate matrix QCs, or previously prepared and qualified urine QCs. MATERIALS [00159] Non-Standard Apparatus and Materials [00160] For standard laboratory procedures, equipment is sourced from appropriate suppliers and will be considered suitable for purpose. Study specific equipment that can be used for this method is detailed as follows: Reference Materials Reference Material Name ^{Alternate Name(s)} ( _{if applicable)} Supplier Reagents Reagent Name Specifications S [00161] Preparation of Reagents [00162] Reagents are prepared in glass bottles and stored at room temperature unless stated otherwise. Mix all reagents thoroughly after preparation. Ethyl Acetate: 2- Combine 980 mL of Ethyl Acetate and 20 Propanol (98:2) [R03] mL of 2-Propanol. [00163] Preparation of Analyte Stock Solutions [00164] Tetranor-PGEM Stock Solution (100 µg/mL) [AS1] [00165] Stock standard solutions for Tetranor-PGEM [AS1] are received from the manufacturer in solutions with certified concentrations (100 μg/mL) in methyl acetate. The certified concentration, storage condition and the expiration date from the Certificate of Analysis (CoA) are applied to the un-opened vials. When using reference standard in this liquid form, a stock evaluation is not required and intermediates for calibration standards and quality control (QC) samples can be prepared from the same stock solution. [00166] Preparation of Internal Standard Stock Solutions [00167] Tetranor-PGEM-d6 Stock Solution (100 µg/mL) [IS1] [00168] Predissolved Tetrano-PGEM-d6 can be used directly or conducting appropriate dilution using Methanol to achieve the final concentration of 100 μg/mL. Container: Glass Storage temperature: Nominal -70°C Expiry: Assigned 365 days expiration [00169] Preparation of Solutions for Comparison and/or Stability Evaluations [00170] Make a separate comparison solution for each stock solution being compared, as shown below. Solution Source Source Source Sol Diluent Final Final ID Solution ution Solution Diluent Concentration Volume Used Volume Volume Concentration [00 p y. ate stability of the highest drug intermediate solution. LIT is used to evaluate stability of the lowest drug intermediate solution. IWC is used to evaluate ISTD working solution stability. [00172] Inject appropriate solutions using a sample analysis method as outlined herein. Mean peak area ratios for each solution and the percent difference of the means are calculated. Container: Glass Storage temperature: Refrigerated Expiry: Assigned one-week expiration Preparation of Analyte Intermediate Solutions Source Source Source Diluent Final Container: Glass Diluent: Methanol Storage temperature: Nominal -70°C Expiry: Assigned 0 days * (but keep for stability testing). * Stability is determined in validation. Preparation of Internal Standard Intermediate Solutions Intermediate Source Source Source Solution S Diluent Final Final S l ti n ID Solution olution Diluent C n ntr ti n V l m U d Volume Volume Concentration Diluent: Methanol: Water (50:50) [R06] Storage temperature: Nominal -70ºC Expiry: Assigned 365 days expiration Preparation of Calibration Standards (Prepared in Surrogate Matrix) Source Source Source Solution Solution Diluent Final Final Concentration Container: Polypropylene D ^iluent: _{Surine Negative Urine Control [SUR]} Other requirements: Sub-aliquot (suggested ≥ 800 µL) Preparation of Surrogate Matrix Quality Control (QC) Samples Source Source Container: Polypropylene D ^iluent: _{Surine Negative Urine Control [SUR]} Other requirements: Sub-aliquot (suggested ≥ 800 µL) Preparation of Urine Quality Control (QC) Samples [0 0173] Endogenous concentration level can be determined in two batches prior to spiking. [00174] † Volume or concentration can be determined based on urine endogenous level. The components are chosen to maximize the urine content while achieving the target final concentration and using workable volumes. [00175] The urine component is ≥ 95% of the final volume for the HQC, MQC and DQC. [00176] The urine component can be < 95% for LQC QC due to endogenous levels. [00177] Ensure that the target final concentration is achieved to 3 significant figures. Final concentration = { [(source conc A)*(vol A)] + [(source conc B)*(vol B)] } Final volume [00178] As an example, if the urine had endogenous concentration of 4.00 ng/mL, then an example MQC could be made as: Final concentration = { [(5000 ng/mL)*(0.0360 mL)] + [(4.00 ng/mL)*(4.959 mL)] } (0.360 + 4.959 mL) = 40.007 ng/mL which rounds to 40.0 ng/mL at 3 significant figures. Preparation of Additional Intermediate Solutions Container: Amber glass vial Diluent: Methanol: Water (50:50) [R06] Expiry: Prepared fresh. Preparation of Recovery and Matrix Effect Samples Container: Amber glass vial Diluent: Methanol:Water (30:70) [R01] Expiry: Prepare fresh. Post extraction spiking procedure for Recovery and Matrix Effects samples [00179] For matrix effect: [00180] Extract 3 BLK RGT samples with no ISTD (add Methanol: Water (50:50) [R06] instead in step 6 of the extraction procedure), and extract blank urine (from 6 different lots) with no ISTD (add Methanol: Water (50:50) [R06] instead in step 6 of the extraction procedure). These samples are reconstituted with 200 µL of the IRS solution in place of the 200 µL of R01 in Step 15 of the extraction procedure. [00181] For Recovery (using ISTD to match Analyte Concentrations): [00182] Extract 3 LQC, 3 MQC, and 3 HQC samples without ISTD (add Methanol: Water (50:50) [R06] instead in step 6 of the extraction procedure). Add 200 µL of the appropriate solution (HIS, MIS, LIS) as described below, in place of the 200 µL of R01 in Step 15 of the extraction procedure. [00183] For ISTD recovery assessment: [00184] Extract 3 QC-Endo samples without ISTD (add Methanol: Water (50:50) [R06] instead in step 6 of the extraction procedure). Add 200 µL of the IRS solution in place of the 200 µL of R01 in Step 15 of the extraction procedure. [00185] HIS is the recovery solution for using the ISTD to match the HQC level. MIS is the recovery solution for using the ISTD to match the MQC level. LIS is the recovery solution for using the ISTD to match the LQC level. IRS is the recovery solution for the internal standard. Preparation of Additional QC Samples Source Source Solution Source Solution Diluent Final Final ID l i l l l i Container: Polypropylene Diluent: * Matrix from 6 different individuals Storage temperature: Nominal -70°C Expiry: Assigned one-week expiration [00186] ^ Endogenous concentration level can be determined in a batch prior to spiking. † Source solution, concentration, or volume, to be determined based on endogenous level. †† Target final concentrations can be selected after endogenous level determination. Parallelism [00187] A set of curves are prepared in one lot of artificial human urine. Three other sets of curves are prepared in three different lots of authentic human urine. Duplicate calibration curves are constructed in each lot of the above matrix. For artificial matrix curve, a linear regression is applied. For authentic matrix curves, linear regression and standard addition approach are used. Endogenous concentration is calculated based on slope and Y-intercept using this formula: |x- intercept| = Endogenous concentration=y-intercept/slope

[00188] Final calibration concentrations is added after analysing the samples and analyse the endogenous concentration of individual lots by using standard addition approach and then adding that endogenous concentration to all eight calibrators.

Container: Polypropylene

Diluent: * Matrix from 3 different individual person’s urine lots.

Storage temperature: Nominal -70°C

Expiry: Assigned one-week expiration

SAMPLE PREPARATION PROCEDURE

[00189] The surrogate matrix Surine Negative Urine Control [SUR] is used for matrix blanks as well as a diluent for samples requiring dilution.

[00190] * Samples (including QC samples) which require dilution: dilute with control matrix e.g. ,100-fold dilution is made by a two-step dilution in which 1) 100 μL of sample/QC to 900 μL of surrogate matrix [SUR], vortex mix (ca.10 seconds) 2) 200 μL of sample/QC to 1800 μL of surrogate matrix [SUR], vortex mix (ca.10 seconds) and take 200 μL for analysis. Alternate dilution scheme can be used. Note: All mixing times are approximate (unless otherwise stated). Automated liquid handling devices include, for example, a Nimbus96.

SAMPLE ANALYSIS [00191] LC Conditions

[00192] Mass Spectrometer Parameters

[00193] Note: Exact mass ions can vary slightly (±0.5 Da) from instrument to instrument because of unit resolution of quadrupole mass spectrometers.

System Evaluation

[00194] A system evaluation can be performed.

Quantitation

[00195] While we have described a number of embodiments of this invention, it is apparent that our basic examples may be altered to provide other embodiments that utilize the compounds and methods of this invention. Therefore, it will be appreciated that the scope of this invention is to be defined by the application and claims rather than by the specific embodiments that have been represented by way of example.