Epithelial ovarian cancer is the fourth most common cause of cancer associated death in woman in the United States. Current therapies offer the promise of a longer and better life for most women with this disease yet few are ultimately cured. This application seeks support for Dr. Michael Seiden, Chairman of the Gynecologic Oncology Research Committee of the Dana Farber Harvard Cancer Center (DF/HCC). Dr. Seiden's long-term career goal is to build a patient-orient translational research program with a focus on the application of novel therapies to women with ovarian cancer. This program includes a high quality clinical research effort and a collateral study of patient material obtained on study or through a linked tumor bank. The other cornerstones of the program also includes mentoring, molecular imaging, and linked laboratory based drug resistance research. Integral to the program is the development of fellows and junior faculty into well trained thought leaders in the field who will then become independent investigators and eventually mentors for their own fellows and junior faculty. The timing of this application coincides with the identification of several junior, yet talented, mentees coupled with a growing translational research effort in ovarian cancer at the Massachusetts General Hospital (MGH) and the Dana Farber/ Harvard Cancer Center (DF/HCC). The research program has three major themes: namely; 1) the evaluation of novel therapeutics targeting the minimization or reversal of drug resistance; 2) the development of a novel molecular imaging program; and 3) the evaluation of molecular mechanisms of intrinsic or acquired drug resistance that may explain mechanisms of therapeutic failure. This grant describes a plan for mentoring and faculty development through the incorporation of mentees into a well supported research program, a structured didactic program, and a rigorous mentoring plan. The P.l.'s dual role as a clinical research director and laboratory P.I. provides fertile opportunity for translation between the clinic and the laboratory. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24CA109416-02
Application #
7090855
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2005-08-01
Project End
2007-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2006
Total Cost
$181,305
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Duan, Zhenfeng; Ames, Rachel Y; Ryan, Meagan et al. (2009) CDDO-Me, a synthetic triterpenoid, inhibits expression of IL-6 and Stat3 phosphorylation in multi-drug resistant ovarian cancer cells. Cancer Chemother Pharmacol 63:681-9
Sakamoto, Hideo; Friel, Anne M; Wood, Antony W et al. (2008) Mechanisms of Cables 1 gene inactivation in human ovarian cancer development. Cancer Biol Ther 7:180-88
Duan, Zhenfeng; Bradner, James; Greenberg, Edward et al. (2007) 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 72:1137-45
Duan, Zhenfeng; Foster, Rosemary; Bell, Debra A et al. (2006) Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer. Clin Cancer Res 12:5055-63
Pieretti-Vanmarcke, Rafael; Donahoe, Patricia K; Pearsall, Lisa A et al. (2006) Mullerian Inhibiting Substance enhances subclinical doses of chemotherapeutic agents to inhibit human and mouse ovarian cancer. Proc Natl Acad Sci U S A 103:17426-31
Duan, Zhenfeng; Bradner, James E; Greenberg, Edward et al. (2006) SD-1029 inhibits signal transducer and activator of transcription 3 nuclear translocation. Clin Cancer Res 12:6844-52