Title:
COMBINATORIAL METHODS FOR INDUCING CANCER CELL DEATH
Document Type and Number:
WIPO Patent Application WO2003016499
Kind Code:
A3
Abstract:
The present invention relates to methods and compositions for inhibiting proliferation and inducing cell death in a population of cancer cells by (i) increasing the amount of the differentiation associated protein MDA-7, and (ii) decreasing RAS activity within the population. It is based, at least in part, on the discovery that decreasing expression of a mutated, activated K-ras gene, together with introducing an expressible mda-7 gene, in pancreatic cancer cells had a synergistic growth-inhibitory and anti-survival effect, and abolished tumorigenicity of the cells in athymic nude mice. The methods of the invention may be directed to the therapy of pancreatic cancer and other malignancies.
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Inventors:
FISHER PAUL B (US)
Application Number:
PCT/US2002/026454
Publication Date:
July 03, 2003
Filing Date:
August 19, 2002
Export Citation:
Assignee:
UNIV COLUMBIA (US)
FISHER PAUL B (US)
FISHER PAUL B (US)
International Classes:
C12N15/09; A61K31/7088; A61K35/76; A61K38/00; A61K38/17; A61K45/00; A61K48/00; A61P35/00; C07K14/47; C12N15/113; C12Q1/02; (IPC1-7): C12N15/63; A61K35/00; A61K38/00; A61K48/00; C07H21/04; C12Q3/00
Foreign References:
| US5543327A | 1996-08-06 |
Other References:
MHASHILKAR A.M. ET AL.: "Melanoma differentiation associated gene 7 (MDA-7): a novel anti-tumor gene for cancer gene therapy", MOLECULAR MEDICINE, vol. 7, no. 4, April 2001 (2001-04-01), pages 271 - 282, XP008013862
SU Z.-Z. ET AL.: "The cancer growth suppressor gene mda-7 selectively induces apoptosis in human breast cancer cells and inhibits tumor growth in nude mice", PROC. NATL. ACAD. SCI. USA, vol. 95, November 1998 (1998-11-01), pages 14400 - 14405, XP002151807
KITA K. ET AL.: "Growth inhibition of human pancreatic cancer cell lines by anti-sense oligonucleotides specific to mutated K-ras genes", INTERNATIONAL JOURNAL OF CANCER, vol. 80, no. 4, February 1999 (1999-02-01), pages 553 - 558, XP002232259
AOKI K. ET AL.: "Suppression of Ki-ras p21 levels leading to growth inhibition of pancreatic cancer cell lines with Ki-ras mutations, but not those without Ki-ras mutation", MOLECULAR CARCINOGENESIS, vol. 20, no. 2, October 1997 (1997-10-01), pages 251 - 258, XP001145717
DING S.-F. ET AL.: "Co-packaging of sense and antisense RNAs: a novel strategy for blocking HIV-1 replication", NUCLEIC ACIDS RESEARCH, vol. 26, no. 13, July 1998 (1998-07-01), pages 3270 - 3278, XP002236827
KOMATA T. ET AL.: "Combination therapy of malignant glioma cells with 2-5A antisense telomerase RNA and recombinant adenovirus p53", GENE THERAPY, vol. 7, no. 24, December 2000 (2000-12-01), pages 2071 - 2079, XP002965377
GAZDAR A.F. ET AL.: "Targeted therapies for killing tumor cells", PROC. NATL. ACAD. SCI. USA, vol. 98, no. 18, 28 August 2001 (2001-08-28), pages 10028 - 10030, XP002965378
SU Z.-Z. ET AL.: "A combinatorial approach for selectively inducing programmed cell death in human pancreatic cancer cells", PROC. NATL. ACAD. SCI. USA, vol. 98, no. 18, 28 August 2001 (2001-08-28), pages 10332 - 10337, XP002965379
See also references of EP 1425399A4
SU Z.-Z. ET AL.: "The cancer growth suppressor gene mda-7 selectively induces apoptosis in human breast cancer cells and inhibits tumor growth in nude mice", PROC. NATL. ACAD. SCI. USA, vol. 95, November 1998 (1998-11-01), pages 14400 - 14405, XP002151807
KITA K. ET AL.: "Growth inhibition of human pancreatic cancer cell lines by anti-sense oligonucleotides specific to mutated K-ras genes", INTERNATIONAL JOURNAL OF CANCER, vol. 80, no. 4, February 1999 (1999-02-01), pages 553 - 558, XP002232259
AOKI K. ET AL.: "Suppression of Ki-ras p21 levels leading to growth inhibition of pancreatic cancer cell lines with Ki-ras mutations, but not those without Ki-ras mutation", MOLECULAR CARCINOGENESIS, vol. 20, no. 2, October 1997 (1997-10-01), pages 251 - 258, XP001145717
DING S.-F. ET AL.: "Co-packaging of sense and antisense RNAs: a novel strategy for blocking HIV-1 replication", NUCLEIC ACIDS RESEARCH, vol. 26, no. 13, July 1998 (1998-07-01), pages 3270 - 3278, XP002236827
KOMATA T. ET AL.: "Combination therapy of malignant glioma cells with 2-5A antisense telomerase RNA and recombinant adenovirus p53", GENE THERAPY, vol. 7, no. 24, December 2000 (2000-12-01), pages 2071 - 2079, XP002965377
GAZDAR A.F. ET AL.: "Targeted therapies for killing tumor cells", PROC. NATL. ACAD. SCI. USA, vol. 98, no. 18, 28 August 2001 (2001-08-28), pages 10028 - 10030, XP002965378
SU Z.-Z. ET AL.: "A combinatorial approach for selectively inducing programmed cell death in human pancreatic cancer cells", PROC. NATL. ACAD. SCI. USA, vol. 98, no. 18, 28 August 2001 (2001-08-28), pages 10332 - 10337, XP002965379
See also references of EP 1425399A4
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