Mechanisms of and therapeutic approaches for overcoming resistance to epidermal growth factor receptor (EGFR)-targeted therapy in squamous cell carcinoma of the head and neck (SCCHN)

Oral Oncology
Katharine A R Price, Ezra E W Cohen

Abstract

The majority of squamous cell carcinoma of the head and neck (SCCHN) overexpress epidermal growth factor receptor (EGFR), which has been associated with poor treatment response and survival. However, only modest success has been achieved with the use of single agents that target EGFR, possibly due to primary and acquired resistance. This review will discuss key mechanisms of and therapeutic approaches to overcoming resistance to EGFR-targeted therapy in SCCHN. Recent preclinical and clinical investigations have demonstrated that other ErbB family receptors (eg, HER2 and HER3) and other horizontal resistance mechanisms, as well as activation of downstream signaling pathways, epigenetic events, and nuclear EGFR, are possible mediators of resistance to anti-EGFR therapeutics. Key downstream pathways that may be implicated in EGFR resistance include phosphatidylinositol-3-kinase/protein kinase B, vascular endothelial growth factor (VEGF), and mammalian target of rapamycin (mTOR). Multiple agents that target EGFR and other ErbB family members (ie, lapatinib, afatinib, and dacomitinib), as well as combination therapies that target EGFR and selected other pathways (eg, VEGF, mTOR, and c-Met) are being investigated clinically. In addit...Continue Reading

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Citations

Sep 11, 2016·Materials Science & Engineering. C, Materials for Biological Applications·Carlos Alberto Kenji ShimokawaRichard Bengt Price
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