Revisiting the ABCs of multidrug resistance in cancer chemotherapy.
The adenosine tri-phosphate binding cassette (ABC) transporters are one of the largest transmembrane gene families in humans. The ABC transporters are present in a number of tissues, providing protection against xenobiotics and certain endogenous molecules. Unfortunately, their presence produces suboptimal chemotherapeutic outcomes in cancer patient tumor cells. It is well established that they actively efflux antineoplastic agents from cancer cells, producing the multidrug resistance (MDR) phenotype. The inadequate response to chemotherapy and subsequent poor prognosis in cancer patients can be in part the result of the clinical overexpression of ABC transporters. In fact, one of the targeted approaches for overcoming MDR in cancer cells is that directed towards blocking or inhibiting ABC transporters. Indeed, for almost three decades, research has been conducted to overcome MDR through pharmacological inhibition of ABC transporters with limited clinical success. Therefore, contemporary strategies to identify or to synthesize selective "resensitizers" of ABC transporters with limited nonspecific toxicity have been undertaken. Innovative approaches en route to understanding specific biochemical role of ABC transporters in MDR and tumorigenesis will prove essential to direct our knowledge towards more effective targeted therapies. This review briefly discusses the current knowledge regarding the clinical involvement of ABC transporters in MDR to antineoplastic drugs and highlights approaches undertaken so far to overcome ABC transporter-mediated MDR in cancer.
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Queens, NY 11439, USA.
Amit K
AK
Tiwari
Kamlesh
K
Sodani
Chun-Ling
CL
Dai
Charles R
CR
Ashby
Zhe-Sheng
ZS
Chen
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents