title: Primary and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer: an update.
abstract: Epidermal growth factor receptor (EGFR) is a critical target in the treatment of nonsmall cell lung cancer (NSCLC). The mutations involving EGFR are more prevalent in patients of Asian ancestry, women, never smokers, and those with adenocarcinoma histology. Primary mechanism of resistance to EGFR-TKIs includes in frame insertion mutation in exon 20, de novo T790M mutation also on exon 20, activating mutations in KRAS, loss of PTEN, and amplification of c-MET whereas acquired resistance results from development of secondary alteration in ATP domain of T790M. There are many novel targeting agents in development to overcome resistance to EGFR TKIs.
authors.affiliation: Penn State Hershey Cancer Institute, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
authors.forename: Ayodele
authors.initials: A
authors.lastname: Ayoola
authors.forename: Amit
authors.initials: A
authors.lastname: Barochia
authors.forename: Kiran
authors.initials: K
authors.lastname: Belani
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000627:therapeutic use; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000077156:Gefitinib