title: EGFR-mutated lung cancer: a paradigm of molecular oncology.
abstract: The development of EGFR tyrosine kinase inhibitors for clinical use in non-small cell lung cancer and the subsequent discovery of activating EGFR mutations have led to an explosion of knowledge in the fields of EGFR biology, targeted therapeutics and lung cancer research. EGFR-mutated adenocarcinoma of the lung has clearly emerged as a unique clinical entity necessitating the routine introduction of molecular diagnostics into our current diagnostic algorithms and leading to the evidence-based preferential usage of EGFR-targeted agents for patients with EGFR-mutant lung cancers. This review will summarize our current understanding of the functional role of activating mutations, key downstream signaling pathways and regulatory mechanisms, pivotal primary and acquired resistance mechanisms, structure-function relationships and ultimately the incorporation of molecular diagnostics and small molecule EGFR tyrosine kinase inhibitors into our current treatment paradigms.
authors.affiliation: Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, New York Presbyterian Hospital- Columbia University Medical Center, New York, NY, USA.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Amy L
authors.initials: AL
authors.lastname: Stiegler
authors.forename: Titus J
authors.initials: TJ
authors.lastname: Boggon
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Balazs
authors.initials: B
authors.lastname: Halmos
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008495:Medical Oncology / Q000379:methods / Q000592:standards; D008954:Models, Biological; D025202:Molecular Diagnostic Techniques / Q000379:methods / Q000592:standards; D058990:Molecular Targeted Therapy / Q000379:methods*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D050505:Mutant Proteins; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors