EGF receptor mutations in lung cancer: from humans to mice and maybe back to humans.
Deletions in exon 19 and nucleotide substitutions in exon 21 are the most common mutations of the EGFR (ErbB1) in NSCLC. These mutations endow the receptor with constitutive kinase activity. Most tumors expressing these mutants respond well to EGFR tyrosine kinase inhibitors, suggesting that they are dependent on mutant EGFR signaling. Two groups developed transgenic mice in which expression of these mutants is temporally induced in mouse lung. Mice expressing EGFR mutants develop bronchioloalveolar cancer and lung adenocarcinoma, which are highly sensitive to EGFR inhibitors. These mouse models provide important opportunities for studying the biology of NSCLC and the refinement of anti-EGFR therapies.
Arteaga
Carlos L
CL
Department of Medicine, Breast Cancer Research Program, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. carlos.arteaga@vanderbilt.edu
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D000068818:Cetuximab; D004318:Doxycycline / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005091:Exons; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011804:Quinolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; C487932:neratinib; D004318:Doxycycline; D000068818:Cetuximab