title: Therapeutic targeting of anaplastic lymphoma kinase in lung cancer: a paradigm for precision cancer medicine.
abstract: The anaplastic lymphoma kinase (ALK) receptor tyrosine kinase was initially discovered as a component of the fusion protein nucleophosmin (NPM)-ALK in anaplastic large-cell lymphoma (ALCL). Genomic alterations in ALK, including rearrangements, point mutations, and genomic amplification, have now been identified in several malignancies, including lymphoma, non-small cell lung cancer (NSCLC), neuroblastoma, inflammatory myofibroblastic tumor, and others. Importantly, ALK serves as a validated therapeutic target in these diseases. Several ALK tyrosine kinase inhibitors (TKI), including crizotinib, ceritinib, and alectinib, have been developed, and some of them have already been approved for clinical use. These ALK inhibitors have all shown remarkable clinical outcomes in ALK-rearranged NSCLC. Unfortunately, as is the case for other kinase inhibitors in clinical use, sensitive tumors inevitably relapse due to acquired resistance. This review focuses on the discovery, function, and therapeutic targeting of ALK, with a particular focus on ALK-rearranged NSCLC.
authors.affiliation: Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan. ryohei.katayama@jfcr.or.jp.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Katayama
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lovly
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts. Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors.forename: Alice T
authors.initials: AT
authors.lastname: Shaw
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D058990:Molecular Targeted Therapy; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors / Q000235:genetics; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases