Riyaz Basha

MD Anderson Cancer Center Orlando, Cancer Research Institute, 6900 Lake Nona Blvd., Orlando, FL 32827, USA

Abstract:

Since patients develop resistance to standard therapies, developing strategies to address such resistance and improving therapeutic efficiency is a serious concern in treating cancer successfully. Small molecules such as non-steroidal anti-Inflammatory drugs (NSAIDs) are known to inhibit cancer cells growth through cyclooxygenesae (COX)-dependent pathways. Recent works from our group and others identified a NSAID, Tolfenamic Acid (TA) with exceptional anti-cancer activity in pre-clinical models. TA acts through COX-independent mechanisms and certainly causes limited toxicity. TA targets Specificity proteins transcription factors and an inhibitor of apoptosis protein (IAP), survivin and inhibits human cancer cell proliferation, tumor growth and metastasis in mouse models for cancer, including the malignancies originating from ovary, pancreas and the central nervous system. Pre-clinical testing using various cancer models showed that TA inhibits cancer cell growth through inducing apoptosis and causing cell cycle arrest. It is also evident that by suppressing IAPs, TA enhances the response of human cancer cells and mouse tumors to radiation therapy and chemotherapy. TA is currently in Phase-I clinical trials at MD Anderson Cancer Center Orlando to test in combination with radiation in patients with upper Gastro-Intestinal cancers. Research from our group demonstrated higher efficacy when TA is combined with radiation or chemotherapy. The underlying mechanisms associated with the response of these combination therapies are currently under investigation utilizing proteomics analysis and molecular profiling approaches. Given that enhancing the responses of standard therapeutic options are highly beneficial in treating cancer, these findings would be crucial in developing novel strategies for treating aggressive malignancies.

Financial Support: Shirley E. Noland Foundation, Hyundai Corporation, Florida Center for Brain Tumor Research, and Ovarian Cancer Alliance of Florida.