title: Molecular pathology of lung cancer: key to personalized medicine.
abstract: The majority of lung adenocarcinoma patients with epidermal growth factor receptor- (EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.
authors.affiliation: Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. liang_cheng@yahoo.com
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Riley E
authors.initials: RE
authors.lastname: Alexander
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Maclennan
authors.forename: Oscar W
authors.initials: OW
authors.lastname: Cummings
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Harvey M
authors.initials: HM
authors.lastname: Cramer
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Davidson
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors