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Hopper-Borge EA , Nasto RE , Ratushny V , Weiner LM , Golemis EA , Astsaturov I
Mechanisms of tumor resistance to EGFR-targeted therapies
Expert Opinion on Therapeutic Targets. 2009 Mar;13(3) :339-362
PMID: 19236156    PMCID: PMC2670612    URL: https://www.ncbi.nlm.nih.gov/pubmed/19236156
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Background: Much effort has been devoted to development of cancer therapies targeting EGFR, based on its role in regulating cell growth. Small-molecule and antibody EGFR inhibitors have clinical roles based on their efficacy in a subset of cancers, generally as components of combination therapies. Many cancers are either initially resistant to EGFR inhibitors or become resistant during treatment, limiting the efficacy of these reagents. Objective/methods: To review cellular resistance mechanisms to EGFR-targeted therapies. Results/conclusions: The best validated of these mechanisms include activation of classic ATP-binding casette (ABC) multidrug transporters; activation or mutation of EGFR; and overexpression or activation of signaling proteins operating in relation to EGFR. We discuss current efforts and potential strategies to override these sources of resistance. We describe emerging systems-biology-based concepts of alternative resistance to EGFR-targeted therapies, and discuss their implications for use of EGFR-targeted and other targeted therapies.
Hopper-Borge, Elizabeth A. Nasto, Rochelle E. Ratushny, Vladimir Weiner, Louis M. Golemis, Erica A. Astsaturov, Igor 228 INFORMA HEALTHCARE; TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND 421OF