Understanding multidrug resistance: identifying the molecular basis of substrate and inhibitor transport by P-glycoprotein (2012-2015)

Cancers expressing the multidrug transporter P-glycoprotein (P-gp) exhibit chemotherapy resistance. The clinical impact of P-gp is so profound that the National Cancer Institute (USA) 'profiles' all anticancer drugs for transport by P-gp, primarily because the precise mechanism by which P-gp binds and transports drugs is currently unknown. The proposal aims to understand, in molecular detail, how different drugs and inhibitors enter and bind to P-gp. To achieve this, a combination of computational modelling techniques and binding assays will be used. The research will provide the information needed to predict how different drugs interact pharmacokinetically with P-gp, a major step in our understanding of P-gp mediated multidrug resistance.