The Clinical Applications of Functional Profiling CSRA: Ovarian Cancer
March 12, 2010 Leave a comment
Ovarian cancer is the leading cause of cancer death for gynecologic malignancies, afflicting 22,000 women in the US each year. The majority of ovarian cancer patients are diagnosed with advanced disease requiring chemotherapy. Experience shows that these patients typically respond well to available drugs, yet there has been no improvement in five-year survival for this disease in decades. And the standard of care — platinum plus taxane — has not changed in more than 15 years.
However, the clinical responsiveness of ovarian cancer renders it an ideal candidate for functional profiling. Using functional profiling, we were the first to use platinum and Gencitabine to treat this disease, showing its efficacy even in platinum-resistant patients. Clinical responses — many very durable — have been observed even in the most heavily pre-treated patients. While there are many drugs active in this disease, microarray gene platforms have been unable to meaningfully distinguish subsets of patients and improve therapy selection. These limitations of DNA-based techniques are not shared by functional profiling, which has the unique capacity to examine complex biological systems in their native state. By incorporating the interaction of tumor cells with their stroma, vasculature and inflammatory elements, functional profiling has been shown to provide highly validated predictive information.
Using functional profiling, we are now exploring novel drug combinations and the introduction of signal transduction inhibitors into the management of advanced ovarian cancer. The failure of large cooperative group clinical trials (like the GOG182) to improve clinical outcomes in the first line setting can now be seen as a failed paradigm of patient randomization. Using functional profiling to examine untreated ovarian cancers, we have shown that no standard combination is best for the majority of patients. Instead, patients manifest unique patterns of sensitivity and resistance that can only be recognized through the individualization of treatment. Functional profiling has the capacity to match patients to available drugs and combinations, thereby improving the odds of good response and minimizing exposure to ineffective and toxic drugs.