2014 Early Career Investigator Grant Recipient — Selvendiran Karuppaiyah, PhD
Project Summary
Ovarian cancer is the most lethal of the gynecological cancers, and treatment is often complicated by diagnosis at late stages and the eventual development of resistance to conventional chemotherapy upon recurrence. Studies conducted by this laboratory over the past 8 years have identified new anticancer compounds which are effective against ovarian cells; even those that have developed resistance to standard chemotherapy. The compounds are unique in that they appear to selectively target cancer cells while sparing noncancerous cells. One of these new compounds has been shown to inhibit the STAT3 signaling pathway, which is critical for ovarian cancer growth and development of therapeutic resistance. Unlike other STAT3 inhibitors, we have shown that the new compounds can be delivered by oral administration, and are readily bioavailable in many tissues of the body in an animal model of ovarian cancer. Testing of these novel inhibitors in hypoxia-mediated, drug resistant ovarian cancer cells and in vivo tumors can be done in a clinically-relevant orthotopic model to evaluate anticancer efficacy. This model allows the investigator to not only evaluate the efficacy of new drugs in treating the primary tumor mass, but also permits investigation into the potential for prevention and/or treatment of metastatic engraftment and growth in nearby tissues and organs. We also propose to continue the bioavailablilty studies and begin to investigate the pharmacokinetic and metabolic breakdown of the compounds as well, in the hopes of eventual progression toward human trials.