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The molecular chaperone heat shock protein 90 (HSP90) plays a crucial role in nuclear factor\u2010\u03baB (NF\u2010\u03baB)\u2010mediated antiapoptosis in ATL cells, and HSP90 inhibitors are new candidate therapeutics for ATL. Accordingly, we investigated the anti\u2010ATL effects of a novel oral HSP90 inhibitor, TAS\u2010116 (pimitespib), and the mechanisms involved in ex vivo and in vivo preclinical models. TAS\u2010116 achieved IC<jats:sub>50<\/jats:sub> values of less than 0.5\u00a0\u03bcmol\/L in 10 ATL\u2010related cell lines and less than 1\u00a0\u03bcmol\/L in primary peripheral blood cells of nine ATL patients; no toxicity was observed toward CD4<jats:sup>+<\/jats:sup> lymphocytes from healthy donors, indicating the safety of this agent. Given orally, TAS\u2010116 also showed significant inhibitory effects against tumor cell growth in ATL cell\u2010xenografted mice. Furthermore, gene expression profiling of TAS\u2010116\u2010treated Tax\u2010positive or \u2010negative cell lines and primary ATL cells using DNA microarray and multiple pathway analysis revealed the significant downregulation of the NF\u2010\u03baB pathway in Tax\u2010positive cells and cell\u2010cycle arrest in Tax\u2010negative cells and primary ATL cells. TAS\u2010116 suppressed the activator protein\u20101 and tumor necrosis factor pathways in all examined cells. These findings strongly indicate the efficacy of TAS\u2010116, regardless of the stage of ATL progression, and its potential application as a novel clinical anti\u2010ATL therapeutic agent.<\/jats:p>","DOI":"10.1111\/cas.15204","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T17:30:08Z","timestamp":1637256608000},"page":"684-696","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["TAS\u2010116 (pimitespib), a heat shock protein 90 inhibitor, shows efficacy in preclinical models of adult T\u2010cell leukemia"],"prefix":"10.1111","volume":"113","author":[{"given":"Emi","family":"Ikebe","sequence":"first","affiliation":[{"name":"Department of Microbiology Oita University Faculty of Medicine Yufu Japan"},{"name":"Department of Safety Research on Blood and Biological Products National Institute of Infectious Diseases Tokyo 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