Targeting multidrug resistance in cancer.
Effective treatment of metastatic cancers usually requires the use of toxic chemotherapy. In most cases, multiple drugs are used, as resistance to single agents occurs almost universally. For this reason, elucidation of mechanisms that confer simultaneous resistance to different drugs with different targets and chemical structures - multidrug resistance - has been a major goal of cancer biologists during the past 35 years. Here, we review the most common of these mechanisms, one that relies on drug efflux from cancer cells mediated by ATP-binding cassette (ABC) transporters. We describe various approaches to combating multidrug-resistant cancer, including the development of drugs that engage, evade or exploit efflux by ABC transporters.
Szakács
Gergely
G
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest Karolina út 29; H-1518 Hungary.
Paterson
Jill K
JK
Ludwig
Joseph A
JA
Booth-Genthe
Catherine
C
Gottesman
Michael M
MM
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents