Drug conjugates and delivery systems targeting carbonic anhydrase IX for treatment of hypoxic tumors
Ahmed Shabana – Graduate Student, Pharmaceutical Sciences, Temple University School of Pharmacy; Md. Abu Sufian – Graduate Student, Pharmaceutical Sciences, Temple University School of Pharmacy
Professor Temple University School of Pharmacy Philadelphia, Pennsylvania, United States
Introduction: Many solid tumors follow Gompertzian growth, outpace angiogenesis and become hypoxic. Persistent hypoxia leads to activation of HIF-1a, which upregulates glucose transporters, glycolytic enzymes and carbonic anhydrase IX (CA IX). CA isozymes move out glycolytic protons, maintaining hypoxic tumor homeostasis, with a key role played by CA IX. We determined the dynamic of CA IX expression under normoxic/hypoxic conditions, and we translated the most potent warheads into targeting moieties and optimized drug delivery systems aimed at hypoxic tumors expressing CA IX.
Learning Objectives:
Assess the expression of carbonic anhydrase IX epitope in different carcinomas under normoxia/hypoxia
Evaluate the CA IX targeting warhead potency and selectivity
Assess CA IX-targeted nanoplatforms for delivery of doxorubicin, reduce chemoresistance, maximize tumor killing.
