Satyamaheshwar Peddibhotla, Ph.D., a research assistant professor of pharmacodynamics, and Siobhan Malany, Ph.D., an associate professor of pharmacodynamics, have been awarded a two-year NIH/NCI, R21 grant (MPI, 1R21CA270714-01) to investigate, “Preclinical development of CXCR6 antagonists to target sorafenib resistance in Hepatocellular Carcinoma.” The project involves synthesis, SAR and lead optimization of SBI-457, a first-in-class in vivo chemokine receptor CXCR6 antagonist they developed previously. The optimized lead molecules will then be evaluated in their potential to overcome resistance and the negative health outcomes of sorafenib therapy in cellular and animal models in collaboration with Ali Zarrinpar, M.D., Ph.D., in the UF College of Medicine. The team includes Morgan Reeves, a third-year graduate student and Alka Mehta, a biological scientist.
Sorafenib (Nexavar®) is an FDA approved first-line treatment for non-resectable hepatocellular carcinoma (HCC), however, therapy is limited due to a moderate life extension, low response rate, serious adverse events and resistance which promotes tumor rebound, proliferation and metastasis. Overexpression and hyperactivation of Chemokine receptor CXCR6, drives sorafenib resistance through aberrant downstream cell signaling which the team seeks to rectify with CXCR6 antagonists.