Novel strategies, based on recent advances in our understanding of tumor development at the molecular genetic level, and aimed at improving our abilities to detect tumor cells in cancer patients, can be important not only for early diagnosis, but also during the period following completion of therapeutic protocols. Such techniques can help distinguish disease-free patients from those harboring residual tumor cells and thus likely to benefit from further therapeutic interventions. Ovarian carcinoma, one of the deadliest of all gynecologic cancer, is particularly amenable to such strategies because these tumors usually remain confined to the abdominal and pelvic cavities, even at advanced disease stages. Currently, 24-54% of women treated for advanced ovarian carcinoma and thought to be free of disease based on the most sensitive techniques currently available eventually experience disease recurrences, highlighting the poor sensitivity of these conventional approaches. We hypothesize that testing for the presence of an enzyme called telomerase, which is strongly associated with the cancer phenotype, can provide a means of increasing our sensitivity to detect residual viable ovarian cancer cells in abdominal washing from patients after completion of adjuvant chemotherapy. This hypothesis is strongly supported by our recent published data We will test this hypothesis in 500 abdominal washings obtained from patients undergoing second-look laparotomies at either USC or six other collaborating institutions across the US. Factors affecting the sensitivity and specificity of this approach for ovarian cancer detection and for predicting recurrences will be defined and characterized. We will also examine the role of steroid and gonadotropin hormones as well as of chemotherapeutic agents on regulation of telomerase expression. The potential influence of these agents on the sensitivity of testing for telomerase as a means of detecting ovarian cancer cells will be examined.
