title: Tyrosine kinase inhibitors for non-small-cell lung cancer: finding patients who will be responsive.
abstract: In recent years, the management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib in patients with mutations in the epidermal growth factor receptor (EGFR). Erlotinib was introduced as a second- and third-line therapy for advanced non-small-cell lung cancer and demonstrated a survival advantage over placebo in unselected patients. Gefitinb did not confer the same advantage but specific subgroups of patients obtained higher response rates. The discovery of EGFR mutations explained the molecular mechanism of sensitivity to TKIs, and several clinical trials have evaluated the efficacy of TKIs in EGFR-mutated patients. New molecular alterations involving different genes have also been described and associated with sensitivity or resistance to TKIs. The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to erlotinib and gefitinib.
authors.affiliation: Human Pathology Department, Medical Oncology Unit, University of Messina, Italy.
authors.forename: Mariacarmela
authors.initials: M
authors.lastname: Santarpia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Altavilla
authors.forename: Maria F
authors.initials: MF
authors.lastname: Salazar
authors.forename: Ignacio
authors.initials: I
authors.lastname: Magri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pettineo
authors.forename: Sara
authors.initials: S
authors.lastname: Benecchi
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D058990:Molecular Targeted Therapy; D009154:Mutation; D018579:Patient Selection; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human