Why Your Support Translates into Hope.

To date, there are no effective blood tests or radiographic tests to detect and screen for ovarian cancer at an early stage. Yet, ovarian cancer has several unique features and challenges that distinguish it from other cancers and serve as the foundation of a coordinated ovarian cancer research program. This understanding of what makes ovarian cancer different also gives us reason to hope for advances that will lead to earlier detection and more effective treatment.

Here’s what we know:

• We need a reliable screening test to detect ovarian cancer at an early stage.
  
  
• There is a unique spread pattern of ovarian cancer characterized by the cancer remaining relatively "confined" to the abdominal cavity.
  
  
• Ovarian cancer has very high sensitivity at initial diagnosis to a specific chemotherapy drug called Cisplatin.
  
  
• There are known genes that may contribute to ovarian cancer’s development such as BRCA-1 and BRCA-2. Testing is available to identify these genes. This is particularly important for women with a family history of the disease.
  
  
• We have knowledge that other genes likely play a role in the development of ovarian cancer.
  
  
• Some ovarian cancer cells are able to be "seen" and recognized by the immune system.

Looking to the future.

Ovations for the Cure has awarded grants to organizations such as Dana-Farber Cancer Institute and Brigham and Woman's Hospital. These talented investigators are working to develop tissue and serum biomarkers that will enable early detection, diagnosis and treatment. They are developing new, targeted therapies for the disease while trying to better understand why ovarian cancer cells are initially sensitive to Cisplatin. Also, investigators are focusing on quality of life research and studying how women make critical treatment decisions.

The future holds great promise through the work of the following scientist physicians:

Ursula Matulonis, M.D.
Director, Medical Gynecologic Oncology
Assistant Professor of Medicine
Department of Medical Oncology
Dana-Farber Cancer Institute

Dr. Matulonis is the Director of Medical Gynecologic Oncology at Dana-Farber Cancer Institute. She is working to develop new therapeutic agents for the treatment of ovarian cancer, to decipher the differences between premenopausal and postmenopausal ovarian cancer and to better understand how patients with ovarian cancer make medical decisions. She is also working to improve the quality of life for ovarian cancer patients. Dr. Matulonis is pursuing efforts to determine a proteomic or protein profile of patients with newly diagnosed ovarian cancer in order to try to predict prognosis, to make rational decisions about adding other more "targeted" treatments to chemotherapy, and to determine why ovarian cancer is very sensitive initially to the drug Cisplatin. Dr. Matulonis is currently collaborating in the testing of a new type of drug, PARP inhibitors, against recurrent ovarian cancer.

At Dana-Farber Cancer Institute, Dr. Matulonis started the tissue and clinical information bank, runs the clinical trials program in gynecologic cancers, and is the principal investigator of several clinical trials. She is also the Medical Director of the Database Mapping Research Project for the Madeline Franchi Ovarian Cancer Research Fund.

Marc Butler, M.D.
Assistant Professor of Medicine
Dana-Farber Cancer Institute

Dr. Butler is focusing on the generation of immunity for cancer therapy. In the clinic, Dr. Butler has recently completed a Phase I trial where ovarian cancer patients were vaccinated with their own tumor cells that were genetically modified to make GM-CSF, an immune stimulant. He and his colleagues are also involved in studying the activity of the drug MDX-CTLA4, which acts to block immune suppression.

Currently, Dr. Butler is working on generating anti-tumor T cells that could then be infused into patients as an anti-cancer therapy. Anti-tumor T cells, sometimes called cytotoxic T cells (CTL), are a promising reagent since they have finely tuned specificity to kill tumor cells while leaving normal cells unharmed. The laboratory focus is to develop a method for growing cancer specific CTL in the laboratory which can then be infused into patients for treatment. One very interesting antigen is NY-ESO-1. Dr. Butler plans to further describe baseline antibody and T cell responses to NY-ESO-1 in ovarian cancer patients and examine the effects of vaccinating ovarian cancer patients against NY-ESO-1 relative to our ability to generate clinically relevant numbers of anti-NY-ESO-1 T cells.

Ronny Drapkin, M.D., Ph.D
Assistant Professor of Medicine
Dana-Farber Cancer Institute
Brigham and Women’s Hospital

Dr. Drapkin’s laboratory effort has focused on the biomarker HE4 (Human Epididymis protein 4). He has shown that this protein is both secreted by ovarian cancers and can be found in the blood of patients with ovarian cancer. Dr. Drapkin is addressing whether HE4 has other roles besides being a biomarker. There is preliminary data indicating that suppression of the HE4 protein in ovarian cancer cells (by a methodology called RNA interference) results in a decrease in the growth capacity of these tumor cells. These results suggest that HE4 may be playing an active role in ovarian cancer pathogenesis and/or progression and may be a novel therapeutic target.

Dr. Drapkin has shown that HE4 is expressed in the two major subtypes of ovarian cancer (serous and endometrioid carcinoma). Interestingly, HE4 is not expressed by other, more common, cancers such as breast, colon, thyroid, kidney, lung. Thus, it appears to be unique to ovarian cancer.

Dr. Drapkin plans to do the following:

• Determine how HE4 expression is regulated by ovarian cancer cells.
  
  
• Determine whether other genes with structural similarities to HE4 are also over-expressed by ovarian cancers.
  
  
• Develop the infrastructure for a biorepository for the collection of patient specimens to be used in the development of biomarkers in collaboration with Dr. Matulonis.

Elizabeth Garner, M.D.
Assistant Professor of Medicine
Department of Obstetrics and Gynecology
Brigham and Women’s Hospital

Dr. Garner is primarily interested in the identification and characterization of genes important in the development of ovarian cancer. Her laboratory is currently studying the Claudin 4 gene, which is identified as being over-expressed in virtually all types of epithelial ovarian cancer. This gene appears to be important in the development of the disease and is a potential target for therapy. Dr. Garner is also interested in pathogenesis of clear cell and endometrioid tumors of the ovary, as this relates to the potential precursor lesions of endometriosis and endosalpingiosis. The identification of genes important in the development of these specific cancers would provide potential targets for their treatment.

On the basis of this work, Dr. Garner’s lab is working to:

• Characterize the role of Claudin 4 in the development of ovarian cancer.
  
  
• Determine the effectiveness of CPE, a molecule that targets Claudin 4, as treatment of ovarian cancer, both in vitro and in an animal model of ovarian cancer.
  
  
• Identify genes important in the development of endometrioid and clear cell tumors in order to identify potential genes for study.