Cells selected for resistance to a single cytotoxic drug may become cross-resistant to a broad range of drugs with different structures and cellular targets. This phenomenon is called multiple drug resistance (MDR). The MDR proteins (Mdrs) are members of a highly conserved superfamily of ATP-binding cassette transport proteins. Mdr functions as an energy-dependent efflux pump for structurally diverse agents ranging from ions to peptides. It is implicated in the development of the multiple drug resistance observed in human cancer cells following prolonged chemotherapy. The classic form of MDR is associated with an increase in the Mdr protein, but not all cases of MDR can be attributed to a rise in Mdr levels. Mdr-1 is an apical transmembrane protein that is an integral part of the blood-brain barrier and functions as a drug-transport pump transporting a variety of drugs from the brain back into the blood. In the human population, there are 15 polymorphisms in the Mdr-1 gene.

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