Song, Minsoo
Journal of medicinal chemistry
2015May ; 58 ( 9 ) :3672-81.
PMID : 25625428
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Song, Minsoo - New Drug Development Center (NDDC), Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Cheombok-ro, Dong-gu, Daegu 701-310, Korea.
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.
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MESH
Animals, Antibodies, Monoclonal/pharmacology/therapeutic use, Antineoplastic Agents/*chemistry/pharmacology/therapeutic use, Carcinoma, Non-Small-Cell Lung/*drug therapy/enzymology, Clinical Trials as Topic, Humans, Kinesin/*antagonists & inhibitors/chemistry, Lung Neoplasms/*drug therapy/enzymology, Models, Molecular, Protein Conformation
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