title: Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer.
abstract: Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.
authors.affiliation: Hospital Sírio-Libanês, São Paulo, SP, BR.
authors.forename: Gabriel Lima
authors.initials: GL
authors.lastname: Lopes
authors.affiliation: Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, BR.
authors.forename: Edoardo Filippo de Queiroz
authors.initials: EF
authors.lastname: Vattimo
authors.affiliation: Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, BR.
authors.forename: Gilberto de
authors.initials: Gd
authors.lastname: Castro Junior
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D000077156:Gefitinib; D017353:Gene Deletion; D018773:Genes, erbB-1; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D017422:Sequence Analysis, DNA
chemical_list: D000970:Antineoplastic Agents; D005819:Genetic Markers; D011799:Quinazolines; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib