tailieunhanh - The role of ABC transporters in anticancer drug transport
Tumors can be intrinsically drugresistant or develop resistance to chemotherapy. Multidrug resistance can develop by diverse mechanisms including decreased rate of drug uptake, increased drug efflux, alterations in drug metabolism, mutation of drug targets, activation of DNA repair mechanisms and evasion of apoptosis. | Turkish Journal of Biology Review Article Turk J Biol (2014) 38: 800-805 © TÜBİTAK doi: The role of ABC transporters in anticancer drug transport Serhan KARVAR* Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA Received: Accepted: Published Online: Printed: Abstract: The main clinical problem in cancer treatment is the development of multidrug resistance. Tumors can be intrinsically drugresistant or develop resistance to chemotherapy. Multidrug resistance can develop by diverse mechanisms including decreased rate of drug uptake, increased drug efflux, alterations in drug metabolism, mutation of drug targets, activation of DNA repair mechanisms, and evasion of apoptosis. The use of modern genomic, proteomic, bioinformatic, and systems biology approaches has resulted in a substantial increase in our ability to identify molecular mechanisms that are involved in multidrug resistance in cancer and to find drugs that may block or reverse the development of drug resistance. Key words: ABC transporters, cancer, neoplasm, P-glycoprotein, chemotherapy, multidrug resistance, tumor biology 1. Introduction Initial chemotherapy of cancer may prove highly beneficial, nearly annihilating a tumor, but a few resistant cancer cells often survive and proliferate. Despite more aggressive second and third courses of chemotherapy, the remaining drug-resistant cells thrive, displaying increasing resistance to drug therapy and eventually displaying virtual invulnerability to chemotherapy. Chemotherapy may fail because the remaining tumor cells are chemotherapyresistant. One of the main clinical issues in cancer is the development of multidrug resistance (MDR) (Fletcher et al., 2010). Malignant tumors usually consist of mixed populations of cells, some of which are drug-sensitive while others are .
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