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)
作者： Katharine A.R. Price , Ezra E.W. Cohen
DOI: 10.1016/J.ORALONCOLOGY.2015.01.018
关键词:
摘要: The majority of squamous cell carcinoma the head and neck (SCCHN) overexpress epidermal growth factor receptor (EGFR), which has been associated with poor treatment response survival. However, only modest success achieved use single agents that target EGFR, possibly due to primary acquired resistance. This review will discuss key mechanisms therapeutic approaches overcoming resistance EGFR-targeted therapy in SCCHN. Recent preclinical clinical investigations have demonstrated other ErbB family receptors (eg, HER2 HER3) horizontal mechanisms, as well activation downstream signaling pathways, epigenetic events, nuclear are possible mediators anti-EGFR therapeutics. Key pathways may be implicated EGFR include phosphatidylinositol-3-kinase/protein kinase B, vascular endothelial (VEGF), mammalian rapamycin (mTOR). Multiple members (ie, lapatinib, afatinib, dacomitinib), combination therapies selected VEGF, mTOR, c-Met) being investigated clinically. In addition, several phase II III trials continue investigate strategies enhance efficacy
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