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

Molecules

Nagaraju Anreddy²  Pranav Gupta²  Rishil J. Kathawala²  Atish Patel¹  John N. D. Wurpel² 

[1] Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USA;

关键词: tyrosine kinase inhibitors;    ABC transporters;    chemotherapy;    modulators;    multidrug resistance;   

DOI  :  10.3390/molecules190913848

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.