ALK alterations and inhibition in lung cancer

• Published in: Seminars in cancer biology Vol. 42; pp. 81 - 88
• Main Authors: Le, Tri, Gerber, David E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2017
• Subjects: Adenocarcinoma; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Crizotinib; Drug Resistance, Neoplasm - genetics; Humans; Molecular Targeted Therapy; Mutation; Oncogene addiction; Personalized medicine; Precision medicine; Receptor Protein-Tyrosine Kinases - genetics; Receptor, Epidermal Growth Factor - genetics; Targeted therapy; Adenocarcinoma; Crizotinib; Precision medicine; Personalized medicine; Targeted therapy; Oncogene addiction
• ISSN: 1044-579X; 1096-3650
• DOI: 10.1016/j.semcancer.2016.08.007

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.