Multidrug resistance: a role for cholesterol efflux pathways?

Multidrug resistance (MDR) severely impairs the efficacy of cancer chemothe rapy. Several protein transporters that mediate drug export have been ident ified, but additional adaptations appear to be necessary for full-fledged d rug resistance. The cell surface density of caveolae and the expression of the caveolar coat protein caveolin are dramatically increased in MDR cancer cells, Acquisition of MDR might thus be accompanied by upregulation of cav eolin-dependent cholesterol efflux pathways, raising the possibility that t hese same pathways are utilized for delivering drugs from intracellular com partments to the plasma membrane, where drugs can be extruded from the cell s by drug efflux ATPases. The upregulation of caveolin mandates a phenotypi c change of MDR cells in terms of their cholesterol homeostasis and is acco mpanied by loss of important features of the transformed phenotype of MDR c ancer cells.