SPOREs
Ovarian
Projects
Project 4: Defining clinical response genes and proteins in high-risk epithelial ovarian carcinoma
Specific Aims
- Evaluate the expression of a refined list of about 50 transcripts linked to Taxol resistance in cell lines, using either quantitative PCR or immuno-histochemistry in paired primary and recurrent tumor specimens.
- Evaluate the role of Fanconi Anemia (FA)/BRCA gene family in platinum resistance by assessing the expression and function of FA genes in matched sets of germ line, primary, and recurrent ovarian tumor specimens.
- Develop a custom microarray chip prognostic of ovarian cancer outcome, with prospective validation using a new cohort of 80 tumors available through the SPORE.
Publications
Kennedy RD, Chen CC, Stuckert P, Archila EM, De la Vega MA, Moreau LA, Shimamura A, and D'Andrea AD. "Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated." J Clin Invest 2007; 117(5):pg:1440-1449. PMCID: 17431503
Kennedy RD, and D'Andrea AD. "DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes." J Clin Oncol 2006; 24(23):pg:3799-3808. PMCID: 16896009
Spentzos D, Cannistra SA, Grall F, Levine DA, Pillay K, Libermann TA, and Mantzoros CS. "IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer." Endocr Relat Cancer 2007; 14(3):pg:781-790. PMCID: 17914107
Konstantinopoulos P, Spentzos D, and Cannistra SA. "Gene Expression profiling in epithelial ovarian cancer." Nature Clin Prac Oncol in press. PMCID: 18648354
Spentzos D, Levine DA, Kolia S, Otu H, Boyd J, Libermann TA, and Cannistra SA. "Unique gene expression profile based on pathologic response in epithelial ovarian cancer." J Clin Oncol 2005; 23(31):pg:7911-7918. PMCID: 16204010
Duan Z, Bradner J, Greenberg E, Mazitschek R, Foster R, Mahoney J, and Seiden MV. "8-benzyl-4-oxo-8-azabicyclo[3.2.1]oct-2-ene-6,7-dicarboxylic acid (SD-1008), a novel janus kinase 2 inhibitor, increases chemotherapy sensitivity in human ovarian cancer cells." Mol Pharmacol 2007; 72(5):pg:1137-1145. PMCID: 17675586
Comments: Dr. Michael Seiden, who was the co-PI of the SPORE accepted the position of Head of the Fox Chase Cancer Center and left in May 2007. With Dr. Seiden’s departure, Dr. Stephen Cannistra was named the PI of Project 4 and the focus shifted from tumor genes predicting chemotherapy resistance to tumor genes predicting survival. For the continuation phase, a new Project 4 will seek to perform high throughput profiling of mutations in proto-oncogenes in order to better target the most appropriate chemotherapy for each patient.
