Understanding the role of multidrug transporter in chemotherapy resistant cancer

Our research investigates the structural dynamics of ABC transporters, in particular the human multidrug transporter P-glycoprotein. The over-expression of P-glycoprotein in cancers induces chemotherapy resistance, one of the most common causes of cancer-related death. While inhibitors of P-glycoprotein have been developed, all have failed at or before clinical trials due to toxic side effects caused by the disruption of normal P-glycoprotein function. Using computational simulations, we are investigating the mechanism of drug binding by P-glycoprotein and how P-glycoprotein transports drugs across the cell membrane. Understanding the nature of drug binding and determining the physical location of the drug binding sites may help in the development of selective inhibitors that selectively overcome chemotherapy resistance while still retaining endogenous P-glycoprotein function.