title: Progress in Discovery of KIF5B-RET Kinase Inhibitors for the Treatment of Non-Small-Cell Lung Cancer.
abstract: A new chimeric fusion transcript of KIF5B (the kinesin family 5B gene) and the RET (Rearranged during Transcription) oncogene, KIF5B-RET, was found in 1-2% of lung adenocarcinomas (LADCs) in late 2011. Several related clinical trials for non-small-cell lung cancer (NSCLC) with KIF5B-RET rearrangements using existing RET inhibitors, such as lenvatinib, vandetanib, sunitinib, ponatinib, cabozantinib, and AUY922, have been swiftly initiated by the discovery of the KIF5B-RET fusion gene. Anti-RET activity and the status of clinical development of these known RET tyrosine kinase inhibitors (TKIs) for KIF5B-RET fusion-positive NSCLC are discussed. A kinase inhibitor that can target a driver mutation specifically may lead to a superior clinical benefit compared with broad-spectrum kinase inhibitors. In this regard, an analysis of the structure of RET kinase and its complex with known RET inhibitors are also briefly discussed.
authors.affiliation: New Drug Development Center (NDDC), Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Cheombok-ro, Dong-gu, Daegu 701-310, Korea.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Song
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D002986:Clinical Trials as Topic; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C488101:KIF5B protein, human; D016547:Kinesins