Multidrug resistance

Abstract

Resistance of malignant cells to cytotoxic agents is often a limiting factor to successful chemotherapy. The classical multidrug resistance is characterised by overexpression of a membrane protein, P-glycoprotein, which acts like a drug extruding pump reducing accumulation of cytotoxic agents inside malignant cells, thereby preventing their function. Resistance is expressed simultaneously towards several structurally unrelated drugs. P-glycoprotein is also expressed in many normal human tissues, e.g., in the gastrointestinal tract, and this may be the reason for intrinsic resistance observed clinically in cancers derived from certain tissues. More often multidrug resistance is acquired during chemotherapy. The physiological function of P-glycoprotein is still unknown but it may have a role in cellular detoxification and secreting mechanisms. Interest in the phenomenon of multidrug resistance centres on the correlation of P-glycoprotein expression to clinical drug resistance. Another goal is to find mechanisms by which the function of P-glycoprotein as a multidrug transporter is prevented and drug resistance reversed.