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.
Selvendiran Karuppaiyah joined the faculty of The Ohio State University College of Medicine in 2011, where he is currently an Associate Professor in Gynecologic Oncology. He earned his PhD from the University of Madras in India, focusing on cancer therapeutics, then completed his post-doctoral training at Kurume Medical University in Japan, where his research targeted STAT3 in liver cancer. An accomplished researcher with more than 17 years of experience, Dr. Karuppaiyah has been repeatedly recognized for his exceptional contributions to the field of cancer research. Dr. Karuppaiyah received the Young Investigator Award from the Kaleidoscope of Hope (KOH) Foundation in 2008. Additional notable awards include the Ovarian Cancer Research Fund’s Liz Tilberis Scholars Program in 2011 and its subsequent renewal in 2014. After securing funding for his first NCI R01 grant in 2014, he continued to excel, receiving three grants from the Department of Defense Ovarian Cancer Research Program (DOD OCRP) from 2020 to 2021, along with the DOD PRCR Award in 2022.
Dr. Karuppaiyah’s research focuses on TMEM205 and PIAS3 roles in high-grade serous ovarian cancer initiation, alongside investigating exosome-derived protein candidates as early biomarkers for high-grade serous ovarian cancer (HGSOC). Dr. Karuppaiyah has also developed novel TMEM205 inhibitors for ovarian cancer. Collaborating closely with Dr. Cohn, MD, and Dr. Suarez, MD at The Ohio State University, he seeks innovative approaches to evaluate early oncogenic protein expression and extracellular vesicle secretion proteins as potential biomarkers for HGSOC. Dr. Karuppaiyah expects to use this information enhance the understanding of HGSOC tumorigenesis and develop targeted therapeutic approaches.