Roles of multidrug resistance genes in breast cancer chemoresistance.
ATP binding cassette (ABC)-containing drug efflux transporters play important roles in regulating intracellular drug concentrations that determine cell sensitivity to chemotherapeutic agents. Of particular relevance to cancer chemotherapy are the transporters P-glycoprotein (Pgp) encoded by multidrug resistance 1 gene, multidrug resistance protein (MRP), and breast cancer resistance protein (BCRP). More than 80% of currently used antitumor agents can be transported by these three transporters, and overexpression of these transporters renders multidrug resistance to a broad spectrum of antitumor agents. Elevated expression of these transporters is frequently found in breast cancers and correlations with elevated expression of Pgp or MRP1 to chemotherapeutic outcomes have been observed in some cases, suggesting that these transporters may contribute to chemoresistance in breast cancers. However, attempts to modulate the activities of these transporters using reversal agents have met with limited success. Future studies should focus on better understanding of the upregulation mechanisms ofABC transporter genes in breast cancers, and of the pharmacologic mechanisms of transporter-reversal agent interactions. These studies may lead to novel strategies for improving chemotherapeutic efficacies through targeted interventions of these ABC transporters.
Kuo
M Tien
MT
Department of Molecular Pathology, Unit 89, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, USA. tkuo@mdanderson.org
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D019450:Genes, MDR / Q000502:physiology*; D006801:Humans