title: ALK alterations and inhibition in lung cancer.
abstract: The advent of precision medicine in non-small cell lung cancer has remarkably altered the direction of research and improved clinical outcomes. The identification of molecular subsets with differential response to targeted therapies began with the identification of epidermal growth factor receptor mutated tumors in subsets of non-small cell lung cancer (NSCLC). Emboldened by unprecedented response rates to kinase inhibitors seen in that subset, the oncologic community searched for other molecular subsets featuring oncogene addiction. An early result of this search was the discovery of NSCLC driven by activating rearrangements of the anaplastic lymphoma kinase (ALK) gene. In an astoundingly brief period following the recognition of ALK-positive NSCLC, details of the biology, clinicopathologic features, development of targeted inhibitors, mechanisms of therapeutic resistance, and new generations of treatment were elucidated. This review summarizes the current understanding of the pathologic features, diagnostic approach, treatment options, resistance mechanisms, and future research areas for ALK-positive NSCLC.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors.forename: Tri
authors.initials: T
authors.lastname: Le
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: dru.gray@utsouthwestern.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Gerber
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: Adenocarcinoma; Crizotinib; Oncogene addiction; Personalized medicine; Precision medicine; Targeted therapy