Efflux Transporters In Cancer Resistance: Molecular And Functional Characterization Of P-Glycoprotein

Multidrug resistance (MDR) is a phenomenon whereby cells confer drug resistance to structurally and functionally unrelated compounds. P-glycoprotein (P-gp; MDR1 or ABCB1), a member of the ATP-binding cassette transporter superfamily, has been particularly recognized for its contribution to MDR in the field of cancer therapeutics. Elevated expression of P-gp has been documented in various drug-resistant tumors, thereby enabling direct drug efflux and limiting intracellular accumulation of anticancer agents that serve as substrates for this transporter. Regulatory mechanisms that modulate P-gp may additionally influence its functional expression in various cancers. To date, various strategies have been developed to inhibit or block P-gp functional expression, and although many of these strategies show promise, they have yet to demonstrate clinically effective results. Further understanding of the role and regulation of P-gp in the context of cancer will allow the implementation of new approaches to increase the pharmacological efficacy of anticancer drug therapy and ultimately overcome MDR. This chapter summarizes current knowledge on P-gp expression patterns, regulatory mechanisms, and inhibition strategies, with emphasis on their relevance to MDR.