
SPOREs : Organ-Specific SPORE Programs : Ovarian

Dana Farber/Harvard Cancer Center Ovarian SPORE

Daniel Cramer, M.D., Sc.D., Principal Investigator
Brigham and Women's Hospital
Ob/Gyn Epidemiology Center
221 Longwood Ave.
Boston, MA 01225
Tel: (617) 732-4895
Fax: (617)732-4899

For more information on this specific SPORE's institution, please visit: http://www.dfhcc.harvard.edu/spores/ovarian/

SPORE Investigators 2004-2009

David Avigan, M.D., Beth Israel Deaconess Medical Center, Co-PI Project 5
Ross Berkowitz, M.D., Brigham and Women’s Hospital, Co-PI Project 2
Michael Birrer, M.D., Ph.D. National Institutes of Health, Co-PI Project 2
John Blessing, Ph.D.,
Steven Cannistra, M.D., Beth Israel Deaconess Medical Center, Co-PI Project 4
Bruce Chabner, M.D., Massachusetts General Hospital, Co-Invest Admin Core
Daniel W. Cramer, M.D., Sc.D., Brigham and Women’s Hospital, Director
Christopher Crum, M.D., Brigham and Women’s Hospital, Co-Inv Core 3
Immaculata DeVivo, Ph.D., Brigham and Women’s Hospital, Co-Inv Project 1
Ronny Drapkin, M.D., Ph.D., Brigham and Women’s Hospital, Co-Inv Project 3
Judy Garber, M.D., Ph.D., Dana Farber Cancer Institute
Susan Hankinson, Sc.D., Brigham and Women’s Hospital, PI Project 1
Jonathan Hecht, M.D., Dana Farber Cancer Institute, Co-Director Core 3
Carolyn Krasner, M.D., Massachusetts General Hospital, PI Supplement
Donald Kufe, M.D., Dana Farber Cancer Institute, PI Project 5
Hang Lee, B.E., M.S., PhD, Dana Farber Cancer Institute, Statistician
Corrine Lenahan, M.D., Beth Israel Deaconess Medical Center, Co-Invest Project 5
Samual Mok, Ph.D., Brigham and Women’s Hospital, PI Project 2
Cynthia Morton, M.D., Brigham and Women’s Hospital, Co-PI Project 2
Ester Oliva, M.D., Massachusetts General Hospital, Co-Invest Core 3
Bo Rueda, Ph.D., Massachusetts General Hospital, Co-Inv/Core 3
Michael V. Seiden, M.D., Ph.D.,
Steven Skates, Ph.D., Massachusetts General Hospital, PI Project 3
Eugene Sobel, Ph.D.,
Linda Titus-Ernstoff, PH.D, Dartmouth-Hitchcock Medical Center, Co-Inv/Project 1

PROJECT 1. MODIFIABLE RISK FACTORS AND GENE/ENVIRONMENTAL INTERACTIONS IN OVARIAN CANCER

Specific Aims

By free radical damage generated from chronic inflammation, genital exposure to talc increases the risk for ovarian cancer and the association may be more apparent in women with the “null” variant of GSTM1, “slow” variant of NAT2, and “G” variant of MPO.
By protecting against prostaglandin-induced upregulation of aromatase or other mechanisms, ovarian cancer risk is reduced by acetaminophen, ibuprofen, aspirin, or other anti-inflammatory drugs and risk may be modified by genes in CYP2C9, UGT1A6, or aromatase pathways.
By enhancing steroid production, caffeine consumption increases ovarian cancer risk and the association may be modified by menopausal status, cholesterol consumption, hormone use, smoking, or caffeine metabolism involving CYP1A1, CYP1A2, CYP2A6, and NAT2.

Key personnel

Susan Hankinson, Sc.D. (BWH)
Daniel W. Cramer, M.D., Sc.D. (BWH)
Immaculata De Vivo, Ph.D. (BWH)
Linda Titus-Ernstoff, Ph.D. (Dartmouth)

Papers published

Terry KL, Titus-Ernstoff L, McKolanis JR, Welch WR, Finn OJ, Cramer DW. Incessant ovulation, mucin 1 immunity, and risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev 2007;16:30-5.

Gates MA, Tworoger SS, Hecht JL, De Vivo I, Rosner B, Hankinson SE. A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer. Int J Cancer 2007 (Epub ahead of print).

Ye B, Aponte M, Dai Y, Li L, Ho MC, Vitonis A, Edwards D, Huang TN, Cramer DW. Ginkgo biloba and ovarian cancer prevention: Epidemiological and biological evidence. Cancer Lett 2007;251:43-52.

Gates MA, Tworoger SS, Terry KL, Titus-Ernstoff L, Rosner B, De Vivo I, Cramer DW, Hankinson SE. Talc use, variants of the GSTM1, GSTT1, and NAT2 genes, and risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 2008.

Danforth KN, Tworoger SS, Hecht JL, Rosner BA, Colditz GA, Hankinson SE. A prospective study of postmenopausal hormone use and ovarian cancer risk. Br J Cancer 2007;96:151-6.

Tworoger SS, Lee IM, Buring JE, Rosner B, Hollis BW, Hankinson SE. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of incident ovarian cancer. Cancer Epidemiol Biomarkers Prev 2007;16:783-8.

Tworoger SS, Lee IM, Buring JE, Pollak MN, Hankinson SE. Insulin-like growth factors and ovarian cancer risk: a nested case-control study in three cohorts. Cancer Epidemiol Biomarker Prev 2007;16:1691-5.

Tworoger SS, Fairfield KM, Colditz GA, Rosner BA, Hankinson SE. Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. Am J Epidemiol 2007;166:894-901.

Cramer DW, Welch WR, Berkowitz RS, Godleski JJ. Presence of talc in pelvic lymph nodes of a woman with ovarian cancer and long-term genital exposure to cosmetic talc. Obstet Gynecol 2007;110:498-501.

Pinheiro SP, Cramer DW. Non-genomic biomarkers of risk in ovarian cancer. Dis Markers 2007;23:355-66.

Tworoger SS, Lee IM, Buring JE, Hankinson SE. Plasma androgen concentrations and risk of incident ovarian cancer. Am J Epidemiol 2008;167:211-8.

Tworoger SS, Gertig DM, Gates MA, Hecht JL, Hankinson SE. Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer. Cancer 2008;112:1169-77.

Gates MA, Tworoger SS, Terry KL, De Vivo I, Hunter DJ, Hankinson SE, Cramer DW. Breast cancer susceptibility alleles and ovarian cancer risk in two study populations. Int J Cancer 2008 (in press).

Kotsopoulos J, Vitonis AF, Terry KL, De Vivo I, Cramer DW, Hankinson SE, Tworoger SS. Coffee intake, variants in genes involved in caffeine metabolism, and the risk of epithelial ovarian cancer. Cancer Causes Control (in press).

Comments: For the renewal application we plan to continue Project 1 with the focus of exploring whether most risk factors for ovarian cancer operate by enhancing or dampening immunity against the surface glycoprotein and tumor marker, human mucin 1.

PROJECT 2. GENETIC CHANGES IN EARLY STAGE OVARIAN CANCER

Specific Aims

Identify DNA copy number abnormalities (CNA) and differential gene expression in ovarian cancer by cDNA array.
Perform allelotyping on a series of early stage ovarian cancer samples using the single nucleotide polymorphism (SNP)-array-based LOH analysis.
Select and validate candidate genes, which may be used as diagnostic markers for early detection of ovarian cancer
Delineate the pathogenetic pathways and identify prognostic markers for ovarian cancer

Key Personnel

Samuel Mok, Ph.D. (BWH)
Ross Berkowitz, M.D. (BWH)
Michael Birrer, M.D., Ph.D. (NCI)
Cynthia Morton, M.D. (BWH)
Eugene Sobel, Ph.D. (Roswell Park Cancer Institute)
John Blessing, Ph.D. (Roswell Park Cancer Institute)

Publications

Bonome T, Lee JY, Park DC, Radonovich M, Pise-Masison C, Brady J, Gardner GJ, Hao K, Wong WH, Barrett JC, et al. "Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary." Cancer Res 2005; 65(22):pg:10602-10612. PMCID: 16288054*

Birrer MJ, Johnson ME, Hao K, Wong KK, Park DC, Bell A, Welch WR, Berkowitz RS, and Mok SC. "Whole genome oligonucleotide-based array comparative genomic hybridization analysis identified fibroblast growth factor 1 as a prognostic marker for advanced-stage serous ovarian adenocarcinomas." J Clin Oncol 2007; 25(16):pg:2281-2287. PMCID: 17538174

Gagnon A, Kim JH, Schorge JO, Ye B, Liu B, Hasselblatt K, Welch WR, Bandera CA, and Mok SC. "Use of a combination of approaches to identify and validate relevant tumor-associated antigens and their corresponding autoantibodies in ovarian cancer patients." Clin Cancer Res 2008; 14(3):pg:764-771. PMCID: 18245537

Huddleston HG, Wong KK, Welch WR, Berkowitz RS, and Mok SC. "Clinical applications of microarray technology: creatine kinase B is an up-regulated gene in epithelial ovarian cancer and shows promise as a serum marker." Gynecol Oncol 2005; 96(1):pg:77-83. PMCID: 15589584*

Koon EC, Ma PC, Salgia R, Welch WR, Christensen JG, Berkowitz RS, and Mok SC. "Effect of a c-Met-specific, ATP-competitive small-molecule inhibitor SU11274 on human ovarian carcinoma cell growth, motility, and invasion." Int J Gynecol Cancer 2007. PMCID: 18021219

Kwong J, Lee JY, Wong KK, Zhou X, Wong DT, Lo KW, Welch WR, Berkowitz RS, and Mok SC. "Candidate tumor-suppressor gene DLEC1 is frequently downregulated by promoter hypermethylation and histone hypoacetylation in human epithelial ovarian cancer." Neoplasia 2006; 8(4):pg:268-278. PMCID: 16756719*

Lee S, Garner EI, Welch WR, Berkowitz RS, and Mok SC. "Over-expression of hypoxia-inducible factor 1 alpha in ovarian clear cell carcinoma." Gynecol Oncol 2007; 106(2):pg:311-317. PMCID: 17532031

Litkouhi B, Litkouhi B, Fleming E, Welch WR, Berkowitz RS, Birrer MJ, and Mok SC. "Overexpression of CEACAM6 in borderline and invasive mucinous ovarian neoplasms." Gynecol Oncol 2008; 109(2):pg:234-239. PMCID: 18331757

Litkouhi B, Kwong J, Lo CM, Smedley JG, 3rd, McClane BA, Aponte M, Gao Z, Sarno JL, Hinners J, Welch WR, et al. "Claudin-4 overexpression in epithelial ovarian cancer is associated with hypomethylation and is a potential target for modulation of tight junction barrier function using a C-terminal fragment of Clostridium perfringens enterotoxin." Neoplasia 2007; 9(4):pg:304-314. PMCID: 17460774

Mok SC, Elias KM, Wong KK, Ho K, Bonome T, and Birrer MJ. "Biomarker discovery in epithelial ovarian cancer by genomic approaches." Adv Cancer Res 2007; 96:pg:1-22. PMCID: 17161674+

Mok SC, Kwong J, Welch WR, Samimi G, Ozbun L, Bonome T, Birrer MJ, Berkowitz RS, and Wong KK. "Etiology and pathogenesis of epithelial ovarian cancer." Dis Markers 2007; 23(5-6):pg:367-376. PMCID: 18057520

Nishimura S, Tsuda H, Ito K, Jobo T, Yaegashi N, Inoue T, Sudo T, Berkowitz RS, and Mok SC. "Differential expression of ABCF2 protein among different histologic types of epithelial ovarian cancer and in clear cell adenocarcinomas of different organs." Hum Pathol 2007; 38(1):pg:134-139. PMCID: 16996567*

Samimi G, Ozbun L, Johnson M, Mok S, and Birrer MJ. "Biomarkers of mucinous tumors of the ovary." Disease Biomarker 2007; 23:pg:377-387. PMCID: 18057522

Schorge JO, Drake RD, Lee H, Skates SJ, Rajanbabu R, Miller DS, Kim JH, Cramer DW, Berkowitz RS, and Mok SC. "Osteopontin as an adjunct to CA125 in detecting recurrent ovarian cancer." Clin Cancer Res 2004; 10(10):pg:3474-3478. PMCID: 15161704*

Tsuda H, Birrer MJ, Ito YM, Ohashi Y, Lin M, Lee C, Wong WH, Rao PH, Lau CC, Berkowitz RS, et al. "Identification of DNA copy number changes in microdissected serous ovarian cancer tissue using a cDNA microarray platform." Cancer Genet Cytogenet 2004; 155(2):pg:97-107. PMCID: 15571795*

Tsuda H, Bandera CA, Birrer MJ, Hashiguchi Y, Berkowitz RS, and Mok SC. "Cyclin E amplification and overexpression in clear cell adenocarcinoma of the ovary." Oncology 2004; 67(3-4):pg:291-299. PMCID: 15557791*

Tsuda H, Ito YM, Ohashi Y, Wong KK, Hashiguchi Y, Welch WR, Berkowitz RS, Birrer MJ, and Mok SC. "Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray analyses." Clin Cancer Res 2005; 11(19 Pt 1):pg:6880-6888. PMCID: 16203778*

Wang V, Li C, Lin M, Welch W, Bell D, Wong YF, Berkowitz R, Mok SC, and Bandera CA. "Ovarian cancer is a heterogeneous disease." Cancer Genet Cytogenet 2005; 161(2):pg:170-173. PMCID: 16102589*

Ye B, Gagnon A, and Mok SC. "Recent technical strategies to identify diagnostic biomarkers for ovarian cancer." Expert Rev Proteomics 2007; 4(1):pg:121-131. PMCID: 17288520

Ye B, Skates S, Mok SC, Horick NK, Rosenberg HF, Vitonis A, Edwards D, Sluss P, Han WK, Berkowitz RS, et al. "Proteomic-based discovery and characterization of glycosylated eosinophil-derived neurotoxin and COOH-terminal osteopontin fragments for ovarian cancer in urine." Clin Cancer Res 2006; 12(2):pg:432-441. PMCID: 16428483

Comments: Dr. Samuel Mok accepted a Professorship at MD Anderson as of June 2008. Drs. Sobel and Blessing have completed their work. For the new Project 2 in the continuation application, Dr. Ronny Drapkin of the Dana Farber Cancer Institute will describe the molecular changes that occur within the secretory cells of the Fallopian tubes that may lead to the occurrence of high grade serous cancers.

PROJECT 3. IDENTIFYING NOVEL BIOMARKERS OF OVARIAN CANCER WITH APPLICATION TO HIGH RISK WOMEN UNDERGOING RISK REDUCING SALPINGO OOPHORECTOMY.

Specific Aims

Prospectively enroll a large cohort of women at high inherited risk for ovarian cancer who are planning risk reducing salpingo-oophorectomy (RRSO) and accumulate a biorepository of pre-operative and post-operative serum, plasma, and urine specimens. Centralized gynecologic pathology review will identify three sub-groups of women: (i) with occult ovarian cancers, (ii) other ovarian neoplasias, and (iii) no ovarian neoplasias (controls).
Identify novel serum, plasma, and urine biomarkers and their patterns for detecting low volume early stage ovarian cancer and other ovarian neoplasias. Samples collected in Aim 1 will be analyzed for combinations of putative ovarian cancer markers by mass spectrometry and 2D differential gel electrophoresis (2D-DIGE). Non-linear classification analyses will identify the optimal combinations of six putative markers for separating samples between the sub-groups.
The proteins and peptides representing the six peaks/spots in the optimal pattern will be identified through LC-MS/MS, and monoclonal antibodies developed against these proteins and peptides. Immunoassays will be developed from the monoclonal antibodies, which will substantially reduce biomarker quantitation variability. This process will thereby increase separation between the sub-groups, and yield repeatable high precision assays. Biomarkers will be remeasured by these immunoassays in samples from the three sub-groups, and non-linear classification analyses will quantify immunoassay based optimal biomarker classification patterns and their operating characteristics.

Key Personnel

Steven Skates, Ph.D. (MGH)
Judy Garber, M.D., Ph.D. (DFCI)
Ronny Drapkin, M.D., Ph.D. (DFCI)

Publications

Greene MH, Piedmonte M, Alberts D, Gail M, Hensley M, Miner Z, Mai PL, Loud J, Rodriguez G, Basil J, et al. "A prospective study of risk-reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: design and baseline characteristics: a gynecologic oncology group study." Cancer Epidemiol Biomarkers Prev 2008; 17(3):pg:594-604. PMCID: 18349277

Lee Y, Miron A, Drapkin R, Nucci MR, Medeiros F, Saleemuddin A, Garber J, Birch C, Mou H, Gordon RW, et al. "A candidate precursor to serous carcinoma that originates in the distal fallopian tube." J Pathol 2007; 211(1):pg:26-35. PMCID: 17117391++

Menon, U., et al., Innovative approaches to recruitment to multicentre trials - Descriptive Study. British Medical Journal, in press.

Moore, R.C., et al., A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecologic Oncology, in press

Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, Steinhoff M, Messerlian G, DiSilvestro P, Granai CO, et al. "The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass." Gynecol Oncol 2008; 108(2):pg:402-408. PMCID: 18061248

Comments: For the continuation application, Dr. Skates will take advantage of new developments in mass spectrographic profiling of blood proteins at the Broad Institute together with unique specimen sets that we believe will culminate in testing of screening biomarkers in the specimens from the largest trail of screening in the world being conducted in the United Kingdom.

PROJECT 4: MECHANISMS OF PACLITAXEL AND PLATINUM RESISTANCE IN OVARIAN CANCER

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.

Key Personnel

Michael Seiden, M.D., Ph.D. (MGH)
Stephen Cannistra, M.D. (BIDMC)
Alan D’Andrea, M.D. (DFCI)

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 07. 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.

PROJECT 5. IMMUNOTHERAPEUTIC APPROACHES FOR OVARIAN CANCER

Specific Aims

To assess fusions of ovarian carcinoma cells with immature and mature autologous DC by evaluating cytokine production (IL-12, IL-10) and potency of the fusions in generating tumor specific immunity in vitro.
To conduct a Phase I/II trial of the ovarian carcinoma-DC fusion vaccine generated with mature DC and administered with rhIL-12;.
To assess the induction of immunity against ovarian cancer cells and MUC1 in patients treated with the fusion cell vaccine alone and with rhIL-12.
To perform a Phase II trial that will define the immunologic efficacy of the fusion cell vaccine and the rV-MUC1+rV-TRICOM vaccine in the treatment of patients with advanced ovarian cancer who have achieved a complete remission following primary chemotherapy.

Key Personnel

Don Kufe, M.D. (DFCI)
David E. Avigan, M.D. (BIDMC)
Baldev S. Vasir , Ph.D. (DFCI)
Jeffrey Schlom, PH.D. (NCI)

Publications

Vasir, Baldev, Wu Zekui, Crawford Keith, Rosenblatt J, Lenahan C, Bissonnette A, Kufe D, Avigan D. Fusions of Dendritic Cells with Breast Carcinoma Stimulate the Expansion of Regulatory T cells While Concomitant Exposure to IL-12, CpG ODN, and anti-CD3/CD28 Promotes the Expansion of Activated Tumor Reactive Cells. J Immunol 2008;181(1):pg:808-821 PMCID 18566447

Comments: In Project 5, the foundation has been laid for customized individual immune therapy for ovarian cancer in remission. Fusing the patients’ own tumor cells with immune cells and using immune “adjuvants” hold promise for long term control of ovarian cancer that might otherwise develop chemotherapy resistance and relapse.

Career Development Awards:

Sandra Orsulic Ph.D. 2005

Advanced ovarian cancers typically show numerous genetic alterations and chromosomal abnormalities. (double check title)

Daniela Dinulescu, PhD

Career Development Award (8/28/2006-7/31/2008):

Title: Therapeutic Strategies Targeting PI3K Pathway in Human Ovarian Cancer

Ronny Drapkin, M.D., Ph.D.

Career Development Award: (8/28/2006-7/31/2008):

Title: HE4 and WAP Gene Function in Ovarian Pathogenesis

Current Overview - 2009

The Dana Farber Harvard Cancer Center (DF/HCC) Ovarian Cancer SPORE enters its final year of its first five years of funding. Funding for an additional five years will require that the renewal application we submitted in September receives a successful review. This “Competing Continuation” application described our progress in the previous 4 years and set forth our vision for ovarian cancer research for the next 5 years. Progress included more than 60 publications and nearly 40 grants received by SPORE investigators. Scientific advances included progress on identifying modifiable risk factors for ovarian cancer (including bolstering the biologic case against talc as cause of ovarian cancer), establishing that the fimbirated end of the Fallopian tubes may be the source of the most lethal type of ovarian cancer, spearheading the first trial of ovarian cancer screening biomarkers in pre-diagnostic specimens from the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial as well as the first inter-SPORE trial of intraperitoneal Avastin, and beginning our own local trial of an immunologic therapy involving a vaccine that fuses a patient’s immune (dendritic cells) with her cancer cells. Our vision for ovarian cancer research for the next five years includes projects that will capitalize on the advances we have made and address the full range of prevention, early detection, and treatment of ovarian cancer.

Developmental Awards:

Grant Year 2005

Alex Ng, Ph.D. Targeted Therapeutic Development Using Small Molecule Microarray

Zhenfeng Duan, M.D., Ph.D., Preclinical Model to Validate the Il-6 Stat 3 Pathway as a Multidrug Resistance Target in Ovarian Cancer

Towia Libermann, Ph.D., New Approaches for Ovarian Cancer Combination Therapy

Richard Penson, M.D., MRCP, Development of a Molecular Imaging Program in Ovarian Cancer

Grant Year 2006

Rosemary Foster, Ph.D., Identification and Characterization of the Ovarian Cancer Stem Cell

Raina Fichorova, Ph.D., Talc and Ovarian Cancer

Patricia Donahoe, M.D., Response markers to select patients for treatment with Müllerian inhibiting substance

Daniel Cramer, M.D., Susceptibility to late stage serous ovarian cancer assessed by genome-wide SNP screening

Grant Year 2007

Tan Ince, M.D., Ph.D. Analysis of genotype and cell-of-origin effect on ovarian adenocarcinoma phenotype

Patricia Donahoe, M.D., Stem Cell Expression Profiles in Ovarian Cancer

Sandra Orsulic, Ph.D., Oncogenic roles of HOXB13 and its downstream effectors in ovarian cancer.

Alex Ng, Ph.D., Serum autoantibody biomarkers for ovarian cancer

Grant Year 2008

Dimitrios Spentzos, M.D., M.M.Sc., The Nrf2/Keap1 pathway as mediator of platinum resistance in ovarian cancer

John Quackenbush, B.S., M.S., Ph.D., Molecular Fingerprints of Ovarian Cancer and Mechanisms of Drug Resistance

Qing Sheng, Ph.D., Systematic Search for and Validation of Therapeutic targets in Human Ovarian Carcinoma

Samuel Mok, Ph.D. Stromal tumor Microenvironment in Ovarian Cancer Pathogenesis

Grant Year 2009

Bo Rueda & Jeffrey Settleman, Defining the sensitivity of parent and hierarchical subpopulations of short term cultured ovarian cancer cells to anti-cancer agents

Shu-Wing Ng & Ross S. Berkowitz, Targeting microRNA in ovarian cancer