Early Detection and Prevention Program

A lack of early detection or prevention strategies is presently a major cause of poor outcome in ovarian cancer patients. A screening test for ovarian cancer could save many lives. A cure is more than 90 percent if cancer is detected early, but less than 30 percent if the disease is detected late. This is true for most cancers. For example, more than 80 percent of women survive breast cancer, because most breast cancers are diagnosed early. By contrast, most ovarian cancers are diagnosed late. If we could achieve early diagnosis, mortality from ovarian cancer could be as low as for breast cancer.

Research Laboratory Activities
The research laboratory activities of the Early Detection & Prevention Program focus on improving the outcomes of ovarian cancer by facilitating earlier detection. These include the development of new blood tests, new imaging tools and other innovative techniques to detect ovarian cancer early. The Center focuses also on reducing the occurrence of ovarian cancer through the development of prevention methods. These include identification of risk factors, exploration of environmental causes of ovarian cancer and development of preventive treatments including a vaccine.

This program encompasses more than ten Penn and Penn-affiliated research laboratories of scientists working on:

• Biomarker discovery
• Antibody and bioassay development
• Molecular imaging including ultrasound, PET nuclear imaging, optical imaging and MRI
• Virology
• Tumor immunology and vaccine development
• Tumor biology

The program is also composed of a group of distinguished Penn epidemiologists, population scientists and clinicians who collaborate to achieve the above goals.

Clinical Activities
The clinical activities of the Early Detection & Prevention Program include a clinic for the screening and prevention of ovarian cancer. Several Penn clinicians and clinical epidemiologists/biostatisticians collaborate on the implementation of clinical trials. The program offers clinical protocols of screening with risk calculation, imaging and molecular testing, and when appropriate, trials of chemoprevention and vaccine prevention.

This new program focuses initially on women with a family history of breast or ovarian cancer or hereditary BRCA1 and BRCA2 gene mutations. These women have a lifetime risk of up to 40 percent (BRCA1) or 20 percent (BRCA2) to develop ovarian cancer and are more likely to die of ovarian cancer than breast cancer in the absence of prevention. Working together with the Cancer Risk Evaluation Program and the Rena Rowan Breast Program, the Ovarian Cancer Early Detection & Prevention Program addresses ovarian cancer specific issues in these women. Furthermore, the program develops protocols for women with other genetic or acquired reproductive conditions that may predispose them to ovarian cancer, working together with the Gastrointestinal Cancer Risk Evaluation Program and the Infertility Program, respectively.

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Advanced Therapeutics Program

In spite of incremental improvements in response rates with the introduction of cisplatin (CDDP), a chemotherapy drug containing platinum; taxanes, anticancer drugs that inhibit cancer cell growth by stopping cell division (e.g. Taxol); and radical surgery, presently, up to 50 percent of patients with advanced ovarian cancer experience complete response to first line chemotherapy. The remaining patients are resistant to platinum or Taxol and become rapidly resistant to all additional available drugs.

Even following complete response, the majority of patients will recur and eventually become resistant to all available chemotherapies. As a result, the mortality from ovarian carcinoma has not changed over the past four decades and half of the patients with advanced ovarian cancer will die within two to three years from diagnosis. It is obvious that alternative therapies are direly needed in ovarian cancer.

Figure 1: Mortality from ovarian cancer (dark purple line) has not really changed over the past few decades despite improved initial response to therapy. Yellow columns show complete response, whilepurple columns show overall response rates. Introduction of cisplatin (CDDP), radical surgery and taxanes have produced small incremental improvement of short lived responses but not cures. Recently intraperitoneal chemotherapy (IP chemo) was shown to increase slightly survival but widespread feasibility and long term efficacy remain to be determined.

Research Laboratory Activities
The research laboratory activities of the Advanced Therapeutics Program focus on developing innovative therapies for ovarian cancer, with emphasis on immune and biological therapies. Dr Coukos’ and Carl June, MD’s laboratories have joined forces to develop immune therapy for ovarian cancer including dendritic cell therapeutic vaccines as well as lymphocyte adoptive therapy.

Lymphocyte therapy uses lymphocytes recovered from the patient’s tumor or blood, which are manipulated in the laboratory to acquire the ability to recognize and kill a tumor, expanded to huge numbers, and then re-infused to the patient. This approach is expected to bring major contributions to ovarian cancer and it is based on the discovery in Dr Coukos’ lab that ovarian cancer is immunogenic, meaning it can be recognized and attacked by lymphocytes

Additional investigators are working towards developing novel therapeutic approaches in ovarian cancer. Dr Jerry Glickson is engineering chemotherapy-loaded nanoparticles that target specifically ovarian cancer cells, in order to develop new ways to deliver chemotherapy to tumors with increased efficacy and reduced toxicity. Dr. Gimotty and Coukos are working to identify tumor markers that will enable them to select patients for individualized therapy.

Clinical Activities
The clinical activities of the Advanced Therapeutics Program conduct clinical trials to test novel therapies emerging from the laboratory. The facilities for the new clinical program will be housed in the Perelman Center for Advanced Medicine, expected to open in 2008.

Cellular therapeutics are prepared at the Penn Cell and Vaccine Production Facility, directed by Bruce Levine, MD. Therapies expected to go to the clinic within 12 to 24 months include lymphocytes recovered from tumors and processed in the laboratory to develop potent tumor-killer cells; lymphocytes modified with gene therapy approaches to recognize and kill tumors and potent tumor vaccines.

Clinical investigators at Penn are also testing the latest in chemotherapy and targeted molecular therapy for ovarian cancer. Penn Gynecologic Oncology is a member of the Phase I/II program of the Gynecologic Oncology Group, a national organization running clinical trials in ovarian cancer. The Ovarian Cancer Center tests new chemotherapy drugs compounds with promising activity in ovarian cancer. Furthermore, the Developmental Therapeutics Program, directed by Peter J. O'Dwyer, MD, works to test the effectiveness of new drugs in treating cancer. Through clinical trials, the team is testing novel compounds in ovarian cancer, including combinations of drugs that shut off the blood supply to tumors with chemotherapy at a dosage that patients can tolerate.

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Ovarian Cancer Biology and Pathogenesis Program

The Ovarian Cancer Biology and Pathogenesis Program has a fundamental discovery focus with the aim to understand the pathogenesis and biology of ovarian cancer. Several multi-disciplinary laboratories focus on various aspects of ovarian cancer genomics, genetics, immunology and biology.

The discoveries within the laboratories are crucial for the Early Detection and Prevention Program as well as the Advanced Therapeutics Program.

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Need an appointment? Request one online 24 hours/day, 7 days/week or call 800-789-PENN (7366) to speak to a referral counselor.

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