title: Mutations and response to epidermal growth factor receptor inhibitors.
abstract: 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.
authors.affiliation: Université Paris Descartes and INSERM, U775, Bases moléculaires de la réponse aux xénobiotiques, Paris, France. pierre.laurent-puig@parisdescartes.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Laurent-Puig
authors.forename: Astrid
authors.initials: A
authors.lastname: Lievre
authors.forename: Hélène
authors.initials: H
authors.lastname: Blons
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005784:Gene Amplification; D011905:Genes, ras; D006801:Humans; D020935:MAP Kinase Signaling System; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics
chemical_list: D047428:Protein Kinase Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase