Abstract:
:Cancer cells are permanently 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 these mechanisms is the overexpression of ATP-binding cassette (ABC) drug efflux pumps leading to multidrug resistance (MDR) of cancer cells through an 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 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 focus on CS agents specifically targeting MRP1 which becomes, when overexpressed, the so called "Achilles' heel" of multidrug resistant cancer cells. We discuss the link between the prominent role of glutathione translocation and related 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.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Lorendeau D,Dury L,Nasr R,Boumendjel A,Teodori E,Gutschow M,Falson P,Di Pietro A,Baubichon-Cortay Hdoi
10.2174/0929867324666161118130238subject
Has Abstractpub_date
2017-01-01 00:00:00pages
1186-1213issue
12eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-79806journal_volume
24pub_type
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