title: Anaplastic Lymphoma Kinase (ALK) Signaling in Lung Cancer.
abstract: Chromosomal rearrangement in the anaplastic lymphoma kinase (ALK) gene was identified as an oncogenic driver in non-small cell lung cancer (NSCLC) in 2007. A multi-targeted ALK/ROS1/MET inhibitor, crizotinib, targeting this activated tyrosine kinase has led to significant clinical benefit including tumor shrinkage and prolonged survival without disease progression and has been approved by US FDA since 2011 for the treatment of advanced ALK-rearranged NSCLC (Ou et al. Oncologist 17:1351-1375, 2012). Knowledge gained from treating ALK-rearranged NSCLC patients including the presenting clinicopathologic characteristics, methods of detecting ALK-rearranged NSCLC, pattern of relapse and acquired resistance mechanisms while on crizotinib, and the clinical activities of more potent ALK inhibitors has led us to a detailed and ever expanding knowledge of the ALK signaling pathway in lung cancer but also raising many more questions that remained to be answered in the future. This book chapter will provide a concise summary of the importance of ALK signaling pathway in lung cancer. Understanding the ALK signaling pathway in lung cancer will likely provide the roadmap to the management of major epithelial malignancies driven by receptor tyrosine kinase rearrangement.
authors.affiliation: Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology-Oncology, University of California Irvine School of Medicine, 101 City Drive, Bldg 56, RT81, Rm 241, Orange, CA, 92868, USA. Ignatius.ou@uci.edu.
authors.forename: Sai-Hong Ignatius
authors.initials: SI
authors.lastname: Ou
authors.affiliation: MUSC Hollings Cancer Center, Department of Medicine, Division of Hematology-Oncology, Medical University of South Carolina College of Medicine, Charleston, SC, 29403, USA.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shirai
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK breakapart FISH; Anaplastic lymphoma kinase rearrangement non-small cell lung cancer; Chromosomal rearrangement; Crizotinib; Receptor tyrosine kinase fusion positive tumors