Ovarian cancer remains the most lethal of all of the gynecological cancers. Chemotherapy is the preferred treatment method; however, the development of chemoresistance by cancer cells has prevented appreciable improvement in the five-year survival rate. Upon continued recurrence, higher and higher chemotherapy doses are required for treatment, and the undesirable side effects become more pronounced, having a negative effect upon the quality of life of ovarian cancer patients. Recent studies by our lab have suggested that a new class of synthetic drugs, called DAPs (for short), could serve as a potential alternative to common chemotherapy regimens. The DAPs have significant potential, not only as a stand-alone, first line treatment for ovarian cancer, but also as a means of combating and eliminating chemotherapy-resistant cancer cells, as well. A sub-set of these drugs appear to specifically target ovarian cancer cells for elimination, while preventing damage to normal cells and tissues. This selectivity is based upon a specific cellular signaling molecule, STAT3, which is “hyperactivated” in ovarian cancer cells. This hyperactivation of STAT3 contributes to uncontrolled ovarian cancer cell growth, and an enhancement of survival.
For this study, I will continue to investigate the anticancer potential of a number of additional DAP compounds that should prove useful in combating ovarian cancer while providing protection to normal, non-cancerous cells. I will use a number of known ovarian cancer cell lines, both susceptible to chemotherapy treatment and those resistant to chemotherapy, to test the effectiveness of the DAPs. Non-cancerous ovarian epithelial cells will be used to determine toxicity towards normal cells. I will then move on to look into the precise mechanism that the most effective DAPs use to target and destroy cancer cells in both the laboratory and using computer simulations. I will also use these most promising new compounds to treat ovarian cancer in a mouse model of the disease.
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.