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Ratushny V , Astsaturov I , Burtness BA , Golemis EA , Silverman JS
Targeting EGFR resistance networks in head and neck cancer
Cell Signal. 2009 Aug;21(8) :1255-68
PMID: 19258037    PMCID: PMC2770888   
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A core set of oncoproteins is overexpressed or functionally activated in many types of cancer, and members of this group have attracted significant interest as subjects for development of targeted therapeutics. For some oncoproteins such as EGFR/ErbB1, both small molecule and antibody agents have been developed and applied in the clinic for over a decade. Analysis of clinical outcomes has revealed an initially unexpected complexity in the response of patients to these agents. Diverse factors, including developmental lineage of the tumor progenitor cell, co-mutation or epigenetic modulation of genes encoding proteins in an extended EGFR signaling network or regulating core survival responses in individual tumors, and environmental factors including inflammatory agents and viral infection, all have been identified as modulating response to treatment with EGFR-targeted drugs. Second and third generation therapeutic strategies increasingly incorporate knowledge of cancer type-specific signaling environments, in a more personalized treatment approach. This review takes squamous cell carcinoma of the head and neck (SCCHN) as a specific example of an EGFR-involved cancer with idiosyncratic biological features that influence design of treatment modalities, with particular emphasis on commonalities and differences with other cancer types.
Ratushny, Vladimir Astsaturov, Igor Burtness, Barbara A Golemis, Erica A Silverman, Joshua S CA-06927/CA/NCI NIH HHS/United States R01 CA-113342/CA/NCI NIH HHS/United States R01 CA-63366/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review England Cellular signalling Cell Signal. 2009 Aug;21(8):1255-68. Epub 2009 Mar 1.