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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) 13:339-362.
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.
Publication Date: 2009-03-01.
PMCID: PMC2670612
Last updated on Saturday, August 22, 2020