Epidermal growth factor receptor mutations in lung adenocarcinoma

• Published in: Laboratory investigation Vol. 94; no. 2; pp. 129 - 137
• Main Authors: Siegelin, Markus D, Borczuk, Alain C
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.02.2014; Nature Publishing Group US; Nature Publishing Group
• Subjects: 631/208/737; 692/420/755; 692/699/67/1059/2326; 692/699/67/1612; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma of Lung; Drug Resistance, Neoplasm - genetics; Drug Resistance, Neoplasm - physiology; epidermal growth factor receptor; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; ErbB Receptors - physiology; Gefitinib; Gene Expression Regulation, Neoplastic - genetics; Gene Expression Regulation, Neoplastic - physiology; Humans; Laboratory Medicine; lung adenocarcinoma; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; MAP Kinase Kinase 1 - genetics; MAP Kinase Kinase 1 - metabolism; Medicine; Medicine & Public Health; Models, Biological; Mutation - genetics; mutations; pathobiology-in-focus; Pathology; Protein Kinase Inhibitors - therapeutic use; Quinazolines - pharmacology; Quinazolines - therapeutic use; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; resistance mutations; Signal Transduction - physiology; tyrosine kinase inhibitors; tyrosine kinase inhibitors; mutations; epidermal growth factor receptor; resistance mutations; lung adenocarcinoma
• ISSN: 0023-6837; 1530-0307; 1530-0307
• DOI: 10.1038/labinvest.2013.147

Despite tremendous progress in the last decade, lung adenocarcinoma still represents a tumor with unfavorable prognosis when detected at advanced clinical stage. High-stage tumors are not amenable to surgical resection, and therefore systemic therapies are needed to control these tumors to prolong patient survival. In the era of molecular and personalized therapeutics, the discovery of mutations in epidermal growth factor receptor (EGFR) in 15–20% of lung adenocarcinomas and the associated response to EGFR-targeting tyrosine kinase (TK) inhibitors have provided a successful avenue of attack in high-stage adenocarcinomas. In this review, we will provide an overview of the EGFR pathway, review the significant somatic EGFR alterations in lung adenocarcinoma and highlight their implications for treatment. In addition, we will examine pathways by which tumors resist EGFR TK therapy, both as primary nonresponders and by acquired resistance. In doing so, we will examine other oncogenic pathways whose status in tumor samples may impact therapeutic responses despite presence of activating EGFR mutations.