Article

Projet
Protéines ABC, membranes et passage membranaire  
Ahcène BOUMENDJEL,   
Titre
MRP1-dependent collateral sensitivity via cellular GSH depletion: identifying selective modulators and investigating their interest in MRP1-overexpressing multidrug-resistant cancer cells by comparison with other modulators.  
[Full paper ]
Auteurs
D. Lorendeau, L. Dury, R. Nasr, A. Boumendjel, E. Teodori, M. Gütschow, P. Falson, A. Di Pietro, H. Cortay
Edition
Curr. Med. Chem. 2017, 24, 1186-1213.
Année
2017
Résumé
Cancer cells are constantly being selected for survival and proliferation. During this process, tumor cells often co-opt basic physiological mechanisms to protect themselves from toxic chemotherapy. One of thesemechanismsis the overexpression of the ATP-binding cassette (ABC) multidrug efflux pumps leading to drug multidrug resistance (MDR) of cancer cells through increase of drug efflux. In the past 20 years, many efforts were done to circumvent MDR through the inhibition of ABC transporters. A number of inhibitors of these transporters were found but are rarely specific or rationally developed. Beside this approach, a new therapeutic strategy towards eradicating drug resistant tumor cells has recently emerged from the observation that cancer cells expressing a high level of these pumps show an unexpected hypersensitivity, called collateral sensitivity (CS) to a selected subset of chemical compounds. In this review, we target on the multidrug resistance protein 1 (MRP1) and after a non-exhaustively highlighting of some of the most exemplary inhibitors of MRP1 and modulators of its expression, we will focus on CS agents specifically targeting MRP1 which becomes, when overexpressed, the Achilles' heel of the multidrug resistant cell. We discuss the link between the prominent role of GSH translocation and redox balance of the cell and the CS induced by certain types of compounds.The latter are discussed according to their chemical class and perspectives in their development for successful eradication of resistant cancer are proposed.