Sphingolipids and multidrug resistance of cancer cells

Abstract

Multidrug resistance is a dramatic complication that can impede cancer treatment. Some cancer cells can become resistant to a cytostatic agent, survive and develop resistance to most agents available for chemotherapy. As multi-drug resistance is linked to sphingolipid metabolism, manipulating sphingolipid metabolism might be a way to circumvent the sensitization of cancer cells to chemotherapy. Two strategies seem particularly promising. One is to drive sphingolipid metabolism towards the production of proapoptotic lipid ceramide, which leads to cell death, and away from sphingosine-l-phosphate and glucosylceramide, which stimulate proliferation. The other is to alter the expression or activity of multidrug effiux pumps that in many cases supply the molecular basis for multidrug resistance.