Grants & Research

Meet Marsha Rivkin Researchers Funded in 2006

Pilot Studies

Daniela Dinulescu, PhD
Eugene Braunwald Research Center, Harvard Medical Center
Targeted therapeutic strategies and early detection biomarkers in ovarian cancer

Epithelial ovarian cancer is the leading cause of death among gynecological cancers. We will actively discover, identify and validate disease biomarkers associated with early disease. The data collected from these key preclinical studies will be instrumental in designing successful clinical trials involving novel, molecularly targeted therapies and screening means for early detection. This work will allow us to test the efficacy of targeted therapies in ovarian cancer, improve the chemotherapies currently used, and better understand the mechanism of tumor chemoresistance. A sustained research effort in the areas of screening and treatment will dramatically improve the prognosis of ovarian cancer patients, as has been proven in other women's cancers, such as breast and cervical cancers.

Robert Jaffe, MD
University of California San Francisco
Inhibition of Telomerase to Treat Advanced Ovarian Cancer

Telomerase is an enzyme that maintains and protects the ends of chromosomes, the telomeres. While telomerase is constrained in many normal adult cells, a majority of cancers appear to depend on active telomerase for their growth, making this enzyme an attractive target for new anti-cancer therapies. Two telomerase targeting methods have been developed in the laboratory of our collaborator, Dr. Elizabeth Blackburn. Both of these approaches, hairpin siRNA and MT-TER, singly and in combination have been shown to block growth of a variety of cancer cell lines in vitro. The goal of this study is to test the efficacy of these telomerase-targeting approaches in a nude mouse model of human ovarian cancer with ascites and intraperitoneal carcinomatosis developed in our laboratory. Ultimately we hope these new methods will decrease human ovarian cancer burden and ascites and lengthen survival for women with this disease.

Elizabeth Smith, PhD
Fox Chase Cancer Center
Suppression of cyclooxygenase in prevention of menopausal gonadotropin-stimulated ovarian cancer risk

The risk of developing ovarian cancer increases rapidly in the peri- and post-menopausal periods, when ovulation ceases but the reproductive gonadotropin hormones are elevated. These gonadotropins can induce expression of certain enzymes which stimulate an inflammation-like condition that may cause changes in ovarian morphology and may promote cancer. To understand the relationship between menopause and ovarian cancer risk, these studies will investigate in the Wv mouse model, which mimics postmenopausal biology, the importance of ovulation and cyclooxygenase-1 enzyme expression on ovarian cancer development. We will also evaluate the potential to use pharmacological inhibitors of cyclooxygenases to reduce ovarian cancer risk.

Daniela Matei, MD
Indiana University
Atransglutaminase 2 Modulates Sensitivity to Chemotherapy in Ovarian Cancer

The most significant cause of death and illness related to ovarian cancer is its propensity to spread in the abdomen. However, the mechanisms responsible for spread are not known. We discovered that an enzyme called transglutaminase 2 (TG2) is present at high levels in ovarian tumors, in abdominal fluid recovered from patients with cancer and in ovarian cancer cells. We also found that this protein facilitates the spreading and adhesion of ovarian cancer cells to the extra-cellular matrix by modulating the function of beta integrins. We hypothesized by modulating tumor cell interaction with the microenvironment TG2 regulates the process of intra-peritoneal metastasis and the response to chemotherapy. In this proposal we will evaluate the physical and functional interaction between TG2 and integrins in ovarian cancer cells and tumors. This interaction may ultimately alter the way ovarian cancer cells respond to chemotherapy. If TG2 alters sensitivity to chemotherapy, the next step will be to test inhibitors of TG2 in conjunction with chemotherapy.

Cassian Yee, MD
Fred Hutchinson Cancer Research Center
Cellular Adoptive Immunotherapy in Treating Patients With Stage III or Stage IV Ovarian Cancer

Using NY-ESO-1, a previously discovered antigen, Dr. Cassian Yee and Dr. Naomi Hunder, both of Fred Hutchinson Cancer Research Center, are using a new technique to treat patients with late stage ovarian cancer. T cells are collected from eligible patients and responder T cells are enhanced. These are given back to the patient through IV, where the patient's immune system will recognize these cells and use them to fight the existing cancer.

Scientific Scholar Awards

Melissa Fishel, PhD
Indiana University School of Medicine
Enhancement of ovarian cancer to chemotherapeutics agents, cisplatin and TMZ, using small molecules, BG and MX

With the exception of a small percentage of patients presenting with stage IA/IB ovarian cancer, surgery along is inadequate treatment. However, virtually all patients who die from ovarian cancer have intrinsic or acquired platinum-resistant disease. Our overall goal is to improve upon current, and discover novel, chemotherapeutic agent therapy for ovarian cancer. To accomplish this, this study will investigate the modulation of two prominent DNA damaging agents: cisplatin and TMZ. Combination therapy has potential for first-line therapy and/or as second-line therapy for patients who have failed standard platinum plus paclitaxel chemotherapy. The applicability of the TMZ+MX treatment lies in the fact that the therapeutic target, i.e. DNA repair, is expressed in all ovarian cancers, thus circumventing the problem of differential expression by tumor cell subpopulations.

Rosemary Foster, PhD
Massachusetts General Hospital
Identification and Characterization of the Ovarian Cancer Stem Cell

Cancer stem cells have recently been identified in some solid tumors and are thought to drive tumor formation. Most tumors likely contain rare subpopulations of stem-like cells that would serve as critical targets of more clinically effective therapies. Our research experiments are designed to provide both convincing evidence of the existence of the ovarian cancer stem cell and initial characterization of the stem cell population. The isolation and characterization of a purified ovarian cancer stem cell population will provide new information about fundamental ovarian cancer biology leading to identification of specific therapeutic targets and development of more intelligent treatment strategies.

Early Detection & Screening

Our program ensures hundreds of high-risk women in Washington State and the Seattle area will receive screening for ovarian cancer, at no cost to the participant. This program will be the first in the nation to validate newly discovered blood markers, combined with conventional markers. The new blood markers, HE4 and mesothelin, were discovered in Seattle with the support of the Marsha Rivkin Center.