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Molecules 2014, 19(9), 13848-13877; doi:10.3390/molecules190913848

Tyrosine Kinase Inhibitors as Reversal Agents for ABC Transporter Mediated Drug Resistance

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA
Current address: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
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Received: 31 July 2014 / Revised: 25 August 2014 / Accepted: 29 August 2014 / Published: 4 September 2014
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)

Abstract

Tyrosine kinases (TKs) play an important role in pathways that regulate cancer cell proliferation, apoptosis, angiogenesis and metastasis. Aberrant activity of TKs has been implicated in several types of cancers. In recent years, tyrosine kinase inhibitors (TKIs) have been developed to interfere with the activity of deregulated kinases. These TKIs are remarkably effective in the treatment of various human cancers including head and neck, gastric, prostate and breast cancer and several types of leukemia. However, these TKIs are transported out of the cell by ATP-binding cassette (ABC) transporters, resulting in development of a characteristic drug resistance phenotype in cancer patients. Interestingly, some of these TKIs also inhibit the ABC transporter mediated multi drug resistance (MDR) thereby; enhancing the efficacy of conventional chemotherapeutic drugs. This review discusses the clinically relevant TKIs and their interaction with ABC drug transporters in modulating MDR. View Full-Text
Keywords: tyrosine kinase inhibitors; ABC transporters; chemotherapy; modulators; multidrug resistance tyrosine kinase inhibitors; ABC transporters; chemotherapy; modulators; multidrug resistance
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Anreddy, N.; Gupta, P.; Kathawala, R.J.; Patel, A.; Wurpel, J.N.D.; Chen, Z.-S. Tyrosine Kinase Inhibitors as Reversal Agents for ABC Transporter Mediated Drug Resistance. Molecules 2014, 19, 13848-13877.

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