Mutations and Response to Epidermal Growth Factor Receptor Inhibitors

• Published in: Clinical cancer research Vol. 15; no. 4; pp. 1133 - 1139
• Main Authors: Pierre Laurent-Puig, Astrid Lievre, Hélène Blons
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-02-2009
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Cetuximab; Erlotinib; Gene Amplification; Genes, ras; Humans; MAP Kinase Signaling System; Medical sciences; Mutation; Neoplasms - drug therapy; Neoplasms - genetics; Pharmacology. Drug treatments; Phosphatidylinositol 3-Kinases - genetics; Protein Kinase Inhibitors - therapeutic use; Proto-Oncogene Proteins c-akt - genetics; PTEN Phosphohydrolase - physiology; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Tyrosine kinase inhibitor; Genetics; Growth factor receptor; Inhibitor; Mutation; Epidermal growth factor receptor
• ISSN: 1078-0432; 1557-3265
• 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.