The Impact of the Induction of Multidrug Resistance Transporters in Therapies by Used Drugs: Recent Studies

A.      Hilgeroth; M.      Hemmer; C.      Coburger

Abstract

Multidrug resistance (MDR) against groups of therapeutic drugs emerged to a central problem in the treatment of various diseases, i.e. cancer and infectious diseases like HIV or malaria. ABC transporters namely P-glycoprotein (P-gp) and various multidrug resistance associated proteins (MRPs) mainly contribute to the MDR phenomenon in cancer treatment and HIV therapy. Their cellular expression in respective cells like cancer cells lowers the intracellular drug concentrations and thus reasons the cellular resistance. The induction of such efflux pumps occurs during the therapy with drugs which will be affected by the MDR phenomenon as a consequence of the induction. In this review studies which report such drugs-caused inductions will be viewed. The review will cover the literature of recent years and attract attention to this important question in drug resistance. Finally, the discussion will suggest possible strategies to overcome the problem, i. e. by using non-inducing drugs.

Keywords: Drug therapy, efflux pumps, multidrug resistance, MDR modulators, transporter induction studies, transporter substrates, HIV-1 protease inhibitors, ABCB1, tipranavir