Mutations and Response to Epidermal Growth Factor Receptor Inhibitors

作者：Laurent Puig Pierre^*; Lievre Astrid; Blons Helene

来源：Clinical Cancer Research, 2009, 15(4): 1133-1139.

DOI：10.1158/1078-0432.CCR-08-0905

Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for a subgroup of patients with colorectal, lung, head and neck, and pancreatic cancers. In these tumors, the EGFR activation turns on at least five different signaling pathways (RAS/mitogen-activated protein kinase, phospholipase C, phosphatidylinositol 3-kinase/AKT, signal transducer and activator of transcription, and SRC/FAK pathways), which are intimately interconnected, and frequent mutations involving either the receptor itself or downstream effectors have been found. Up to now, it seems that alterations at the EGFR level has major importance in EGFR tyrosine kinase inhibitor response, whereas modifications of downstream effectors could lead to treatment resistance. Furthermore, our understanding of the mechanism of the EGFR network activation provides new hypotheses on potential new anticancer drugs that may be effective.

• 出版日期2009-2-15