Transport proteins in drug resistance: biology and approaches to circumvention

At least two transport proteins, P-glycoprotein (Pgp) and the multidrug resistance associated protein (MRP), are believed to play a significant role in clinical resistance to cytotoxic therapy. These proteins are expressed at relatively high levels in a number of malignant diseases including various types of leukaemias. They are variably expressed on both the plasma membrane and intracellular vesicular membranes resulting in cellular drug efflux or vesicular drug sequestration, respectively. The action of MRP as a drug transporter depends on intracellular levels of glutathione. A number of strategies for circumvention of these drug resistance mechanisms have been developed and some of these are now in clinical trial.