Silencing Ovarian Cancer

Dr. Elvio G. Silva, professor of pathology, examines ovarian cancer slides.

Ovarian cancer often is described as "the silent killer" - and for good reason.

Almost 15,000 American women died last year from ovarian cancer, largely because in the vast majority the disease could not be detected early enough for current treatments to destroy it. A lack of early symptoms usually conceals ovarian cancer until it has spread beyond the ovaries to involve the upper abdomen or distant sites.

"An estimated 26,800 new cases of ovarian cancer are expected during 1997. While accounting for only 4 percent of cancers in women, ovarian cancer causes more deaths than any other gynecological cancer in this country. Right now, about 1.7 women are dying from the disease every hour of every day," says Dr. David M. Gershenson, professor and deputy chairman of the Department of Gynecologic Oncology and holder of the Anderson Clinical Faculty Chair for Cancer Treatment and Research.

Dr. Gershenson directs the Sandra G. Davis Ovarian Cancer Research Program, a comprehensive multidisciplinary initiative that combines the expertise of more than 40 physicians and scientists collaborating in targeted research, which he believes "will finally help turn the corner against this devastating disease."

The ovarian program is different from M. D. Anderson's other new research initiatives in that it is named in memory of a patient who inspired her caregivers to accelerate their efforts to improve the outlook for ovarian cancer.

"She was an exceptional individual who brought great courage and dignity to her four-year struggle with ovarian cancer. This program is the fulfillment of her wish to significantly improve prevention and early detection methods for ovarian cancer and to find better treatments for other women who must fight this disease," Dr. Gershenson says.

He outlines four goals for the coordinated laboratory and clinical research:

· Identification of women at increased risk.

· Development of specific prevention strategies.

· Design of a reliable non-invasive screening test to detect early disease.

· Development of effective therapies for advanced disease.

"This is an ideal time for such an initiative because we have many opportunities to apply emerging molecular and genetic information. Fortunately, we already have a critical mass of experts in multiple fields to translate this new knowledge into therapeutic action," Dr. Gershenson notes.

One promising research project involves identifying patients with defective p53 tumor suppressor genes and designing methods to delete or correct the molecular mutation associated with development of ovarian cancer. About half of ovarian cancers have a mutated p53 gene. Two different techniques, including one similar to a form of gene therapy being studied in some lung cancer patients at M. D. Anderson, soon will be available to ovarian cancer patients for whom conventional chemotherapy failed to eliminate their disease.

Another encouraging project aims to improve current chemotherapy by adding the anti-cancer drugs topotecan and navelbine to Taxol and cisplatin in a more aggressive front-line approach for newly diagnosed patients. Other clinical trials center on designing individualized therapies for patients who did not respond to initial chemotherapy.

"I am optimistic that we will be able to tailor chemotherapy for many patients in the near future. For patients who have failed conventional front-line therapy, we will soon initiate a study to perform a fine needle aspiration biopsy of tumor deposits, then test the cancer cells in a special laboratory assay to see if the cells can be destroyed by one of three drugs. Our aim is to administer the drug with the best chance of success," Dr. Gershenson explains.

Each of the three drugs - topotecan, navelbine and hexalen - has about a 25 percent response rate in refractory ovarian cancers. By giving the optimal drug, he says, many patients may be spared side effects of unsuccessful therapy.

An additional treatment strategy being studied at the cancer center provides gene therapy to make bone marrow more resistant to chemo- therapy for ovarian and breast cancer patients. Known as chemoprotection, this three-phase gene augmentation approach entails removing progenitor or stem cells from patients' bone marrow, manipulating the cells in the laboratory so that when they are returned patients can tolerate high-dose chemotherapy.

A second gene therapy technique involves injecting a "good" gene that in experimental animals reduced the proliferative effect of a cancer-causing gene linked to the aggressive spread of some cancers. In this clinical trial, ovarian cancer patients receive the good E1A gene enclosed in fatty globules called liposomes, which are injected into the abdominal cavity in an attempt to suppress the metastatic action of the HER-2/neu oncogene.

Dr. Gershenson says another segment of the research initiative seeks to determine the role of genetic predisposition for developing the disease. "Only 5 to 10 percent of ovarian cancers are known to occur because of inherited genetic mutations, but women who carry the abnormalities have about a 60 percent lifetime risk for ovarian cancer," he says.

Women who have had breast cancer or who have a strong family history of either breast or ovarian cancer may be at increased risk for ovarian cancer. The discovery of two cancer susceptibility genes, BRCA-1 and BRCA-2, has opened a new avenue for genetic testing. M. D. Anderson's Cancer Prevention Center offers genetic counseling and testing for women thought to have a genetic risk based on family history or race. The latter includes Jewish women of Ashkenazi descent, who have a greater risk of carrying the genes.

One fertile area for earlier detection focuses on finding tumor markers or chemicals that suggest the presence of a small number of cancer cells prior to any other diagnostic method now available. Several of these markers are being evaluated under the direction of Dr. Robert C. Bast Jr., head of the Division of Medicine, whose group hopes to identify combinations of tumor markers that will be useful screening tools.

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