Ovarian Cancer Research
Under the direction of Dr. Beth Karlan, the Gynecologic Oncology Research Laboratory at Cedars-Sinai Medical Center's Burns & Allen Research Institute is pursuing a many-sided approach to understanding the causes and molecular alterations that produce cancers in the female reproductive tract.
The current primary focus of Dr. Karlan's group is ovarian cancer, although the group has conducted experiments on genetic changes related to cervical and endometrial cancers.
As a result of the busy clinical service in gynecologic oncology at Cedars-Sinai, Dr. Karlan has developed an extensive bank of frozen tumor tissues that are used in studies of cancer cell growth. These specimens are analyzed and compared to normal ovarian tissues for genetic changes. Dr. Karlan and her group have developed techniques to grow normal and malignant ovarian epithelial cells in the lab, allowing the group to investigate biologic responsiveness and molecular mechanisms involved in ovarian tumors. The research group's activities include:
- p53 gene therapy for ovarian cancer. The p53 gene plays a key role in controlling cell growth, high frequency of p53 mutations in ovarian cancers and the potential of ovarian cancer to remain confined to the pelvic cavity. The Mary Kay Ash Charitable Foundation and the Ahmanson Foundation fund these studies. In addition to in-lab study, researchers are using the p53 gene in a clinical trial, along with traditional chemotherapy, to treat women with certain forms ovarian cancer. Funded by Schering-Plough Corporation, these studies are being performed in collaboration with Drs. Dennis Slamon and Mark Pegram.
- Ovarian cancer xenograft model systems. Experiments are now being directed toward grafting ovarian cancer cells into mice. Cultures are injected into these animals in several ways. Tumors have been successfully established and have carried through six generations. Survival data is being carefully monitored for use in future experiments. Studies are funded by the Ahmanson Foundation.
- Ovarian cancer screening. The focus of the Gilda Radner Ovarian Cancer Detection Program is to discover effective means to diagnose ovarian cancer at a curable stage. State-of-the-art ultrasound technologies and tumor marker tests are performed on participants on an annual basis. More than 1,200 participants who are genetically at risk for ovarian cancer have taken part in the program since its establishment in 1991. Approximately 20% of this population are of Ashkenazi Jewish decent. These individuals are undergoing BRCA1 and BRCA2 testing. A large serum and DNA bank has been established from this population.
- BRCA1 and BRCA2 in ovarian cancer. In collaboration with Dr. Steven Narod, researchers have been studying the mutation frequency in the BRCA1 and BRCA2 genes in ovarian carcinoma patients of Ashkenazi Jewish decent. To date, more than 80 patients have been studied. Prognosis factors, tumor type and other risks are being evaluated in this analysis.
- Ovarian cancer imaging modalities. In collaboration with investigators at NASA's Jet Propulsion Laboratories, scientists are developing devices to detect ovarian cancer. Work on creating miniature potential detection devices is concurrently ongoing.
- HER-2/neu oncogene studies. In collaboration with Dr. Dennis Slamon, the research laboratory is studying the HER-2/neu oncogene as it relates to regulating steroid hormones in females with ovarian cancer. Currently, analyses of more than 500 Stage III ovarian cancer specimens are underway. Our database includes pathologic data on these patients that will help determine whether the gene puts a woman at greater risk for the disease. This work has been funded in part by the American Cancer Society.
- Stromal-epithelial interactions. This research focuses on techniques to establish surface and primary cultures of normal human ovaries. Using these specimens, researchers are investigating the connection between cell growth and environmental factors. This work has been funded in part by the Concern Foundation.