{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:54:42Z","timestamp":1788317682553,"version":"build-2803163510"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"DOI":"10.1007\/s00280-025-04855-9","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T03:27:15Z","timestamp":1769052435000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Drug\u2013drug interactions with pioglitazone, losartan, and midazolam and anti-tumor efficacy and safety study of TAS-115 in patients with solid tumors"],"prefix":"10.1007","volume":"96","author":[{"given":"Yuki","family":"Katsuya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Takenaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"4855_CR1","unstructured":"World Health Organization Cancer Fact Sheet WHO website. Updated 3 Mar 2021. Accessed 10 (2021) Aug https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer"},{"key":"4855_CR2","unstructured":"International Agency for Research on Cancer. Cancer Tomorrow. http:\/\/gco.iarc.fr\/tomorrow\/home Accessed 10 Aug 2021."},{"key":"4855_CR3","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1002\/2211-5463.12827","volume":"10","author":"N Yasuda","year":"2020","unstructured":"Yasuda N, Takenaka S, Nakai S, Nakai T, Yamada S, Imura Y, Outani H, Hamada K, Yoshikawa H, Naka N (2020) TAS-115 inhibits PDGFR\u03b1\/AXL\/FLT-3 signaling and suppresses lung metastasis of osteosarcoma. FEBS Open Bio 10:767\u2013779. https:\/\/doi.org\/10.1002\/2211-5463.12827","journal-title":"FEBS Open Bio"},{"key":"4855_CR4","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1165\/rcmb.2018-0098oc","volume":"60","author":"K Koyama","year":"2019","unstructured":"Koyama K, Goto H, Morizumi S, Kagawa K, Nishimura H, Sato S, Kawano H, Toyoda Y, Ogawa H, Homma S, Nishioka Y (2019) The tyrosine kinase inhibitor TAS-115 attenuates Bleomycin-induced lung fibrosis in mice. Am J Respir Cell Mol Biol 60:478\u2013487. https:\/\/doi.org\/10.1165\/rcmb.2018-0098oc","journal-title":"Am J Respir Cell Mol Biol"},{"key":"4855_CR5","doi-asserted-by":"publisher","unstructured":"Shibutani T, Goto R, Miyazaki I, Hashimoto A, Suzuki T, Ishida K, Haruma T, Osada T, Harada T, Fujita H, Ohkubo S (2023) Modulation of tumor immune microenvironment by TAS-115, a multi-receptor tyrosine kinase inhibitor, promotes antitumor immunity and contributes anti-PD-1 antibody therapy. Sci Rep 13:8821. https:\/\/doi.org\/10.1038\/s41598-023-35985-w","DOI":"10.1038\/s41598-023-35985-w"},{"key":"4855_CR6","doi-asserted-by":"publisher","unstructured":"6.Shibutani T, Goto R, Miyazaki I, Hashimoto A, Suzuki T, Ishida K, Haruma T, Osada T, Harada T, Fujita H, Ohkubo S. (2024) Author Correction: Modulation of tumor immune microenvironment by TAS-115, a multi-receptor tyrosine kinase inhibitor, promotes antitumor immunity and contributes anti-PD-1 antibody therapy. Sci Rep 14:4784. https:\/\/doi.org\/10.1038\/s41598-024-55488-6","DOI":"10.1038\/s41598-024-55488-6"},{"key":"4855_CR7","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1186\/s12885-017-3324-3","volume":"17","author":"S Yamada","year":"2017","unstructured":"Yamada S, Imura Y, Nakai T, Nakai S, Yasuda N, Kaneko K, Outani H, Takenaka S, Hamada K, Myoui A, Araki N, Ueda T, Itoh K, Yoshikawa H, Naka N (2017) Therapeutic potential of TAS-115 via c-MET and PDGFR\u03b1 signal inhibition for synovial sarcoma. BMC Cancer 17:334. https:\/\/doi.org\/10.1186\/s12885-017-3324-3","journal-title":"BMC Cancer"},{"key":"4855_CR8","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1158\/1535-7163.mct-13-0459","volume":"12","author":"H Fujita","year":"2013","unstructured":"Fujita H, Miyadera K, Kato M, Fujioka Y, Ochiiwa H, Huang J, Ito K, Aoyagi Y, Takenaka T, Suzuki T, Ito S, Hashimoto A, Suefuji T, Egami K, Kazuno H, Suda Y, Nishio K, Yonekura K (2013) The novel VEGF receptor\/MET-targeted kinase inhibitor TAS-115 has marked in vivo antitumor properties and a favorable tolerability profile. Mol Cancer Ther 12:2685\u20132696. https:\/\/doi.org\/10.1158\/1535-7163.mct-13-0459","journal-title":"Mol Cancer Ther"},{"key":"4855_CR9","doi-asserted-by":"publisher","unstructured":"Fujita H, Gomori A, Fujioka Y, Kataoka Y, Tanaka K, Hashimoto A, Suzuki T, Ito K, Haruma T, Yamamoto-Yokoi H, Harada N, Sakuragi M, Oda N, Matsuo K, Inada M, Yonekura K (2016) High Potency VEGFRs\/MET\/FMS Triple Blockade by TAS-115 Concomitantly Suppresses Tumor Progression and Bone Destruction in Tumor-Induced Bone Disease Model with Lung Carcinoma Cells. PLoS One 11:e0164830. https:\/\/doi.org\/10.1371\/journal.pone.0164830.","DOI":"10.1371\/journal.pone.0164830"},{"key":"4855_CR10","unstructured":"Kunii E, Ozasa H, Oguri T, Maeno K, Fukuda S, Uemura T, Takakuwa O, Ohkubo H, Takemura M, Niimi A (2015) Reversal of c-MET-mediated Resistance to Cytotoxic Anticancer Drugs by a Novel c-MET Inhibitor TAS-115. Anticancer Res.35:5241-5247. https:\/\/ar.iiarjournals.org\/content\/35\/10\/5241.long"},{"key":"4855_CR11","doi-asserted-by":"publisher","first-page":"20891","DOI":"10.1074\/jbc.m116.727875","volume":"291","author":"K Watanabe","year":"2016","unstructured":"Watanabe K, Hirata M, Tominari T, Matsumoto C, Fujita H, Yonekura K, Murphy G, Nagase H, Miyaura C, Inada M (2016) The MET\/Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitor also attenuates FMS-dependent osteoclast differentiation and bone destruction induced by prostate cancer. J Biol Chem 291:20891\u201320899. https:\/\/doi.org\/10.1074\/jbc.m116.727875","journal-title":"J Biol Chem"},{"key":"4855_CR12","doi-asserted-by":"crossref","unstructured":"Nakade J, Takeuchi S, Nakagawa T, Ishikawa D, Sano T, Nanjo S, Yamada T, Ebi H, Zhao L, Yasumoto K, Matsumoto K, Yonekura K, Yano S Triple inhibition of EGFR, Met, and VEGF suppresses regrowth of HGF-triggered, erlotinib-resistant lung cancer harboring an EGFR mutation. J Thorac Oncol 9:775\u2009\u2013\u2009783. https:\/\/doi.org\/10.1097\/jto.0000000000000170","DOI":"10.1097\/JTO.0000000000000170"},{"key":"4855_CR13","doi-asserted-by":"publisher","unstructured":"Zhao L, Yasumoto K, Kawashima A, Nakagawa T, Takeuchi S, Yamada T, Matsumoto K, Yonekura K, Yoshie O, Yano S (2014) (2013) Paracrine activation of MET promotes peritoneal carcinomatosis in scirrhous gastric cancer. Cancer Sci 104:1640-1646. https:\/\/doi.org\/10.1111\/cas.12301","DOI":"10.1111\/cas.12301"},{"key":"4855_CR14","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1165\/rcmb.2018-0387ed","volume":"60","author":"CL Wilson","year":"2019","unstructured":"Wilson CL, Hung CF (2019) Another weapon in the battle against idiopathic pulmonary fibrosis? Am J Respir Cell Mol Biol 60:386\u2013387. https:\/\/doi.org\/10.1165\/rcmb.2018-0387ed","journal-title":"Am J Respir Cell Mol Biol"},{"key":"4855_CR15","doi-asserted-by":"publisher","unstructured":"Doi T, Matsubara N, Kawai A, Naka N, Takahashi S, Uemura H, Yamamoto N Phase I study of TAS-115, a novel oral multi-kinase inhibitor, in patients with advanced solid tumors. Invest New Drugs 38:1175\u20131185. https:\/\/doi.org\/10.1007\/s10637-019-00859-4","DOI":"10.1007\/s10637-019-00859-4"},{"key":"4855_CR16","doi-asserted-by":"publisher","unstructured":"Kawai A, Naka N, Shimomura A, Takahashi S, Kitano S, Imura Y, Yonemori K, Nakatani F, Iwata S, Kobayashi E, Outani H, Tamiya H, Naito Y, Yamamoto N, Doi T (2021) Efficacy and safety of TAS-115, a novel oral multi-kinase inhibitor, in osteosarcoma: an expansion cohort of a phase I study. Invest New Drugs 39:1559\u20131567. https:\/\/doi.org\/10.1007\/s10637-021-01107-4","DOI":"10.1007\/s10637-021-01107-4"},{"key":"4855_CR17","doi-asserted-by":"publisher","unstructured":"Matsubara N, Uemura H, Nagamori S, Suzuki H, Uemura H, Kimura G (2020) (2021) A Phase II, Randomized, Open-Label, Multi-arm Study of TAS-115 for Castration-Resistant Prostate Cancer Patients With Bone Metastases. Clin Genitourin Cancer 19:491\u2013500. https:\/\/doi.org\/10.1016\/j.clgc.2021.07.013","DOI":"10.1016\/j.clgc.2021.07.013"},{"key":"4855_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.conctc.2021.100832","volume":"23","author":"Y Nishioka","year":"2021","unstructured":"Nishioka Y, Homma S, Okubo T, Azuma A (2021) Design of phase 2 study of TAS-115, a novel oral multi-kinase inhibitor, in patients with idiopathic pulmonary fibrosis. Contemp Clin Trials Commun 23:100832. https:\/\/doi.org\/10.1016\/j.conctc.2021.100832","journal-title":"Contemp Clin Trials Commun"},{"key":"4855_CR19","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.resinv.2023.04.008","volume":"61","author":"Y Nishioka","year":"2023","unstructured":"Nishioka Y, Homma S, Ogura T, Sato S, Arai N, Tomii K, Kamio K, Sakamoto S, Miyazaki Y, Tomioka H, Hisata S, Handa T, Azuma A (2023) Exploratory phase 2 study of the novel oral multi-kinase inhibitor TAS-115 in patients with idiopathic pulmonary fibrosis. Respir Investig 61:498\u2013507. https:\/\/doi.org\/10.1016\/j.resinv.2023.04.008","journal-title":"Respir Investig"},{"key":"4855_CR20","unstructured":"Director of the Pharmaceutical Evaluation Division Pharmaceutical Safety and Environmental Health Bureau, Ministry of Health, Labour and Welfare. Guideline on drug interaction for drug development and appropriate provision of information dated 23 July 2018 (PSEHB\/PED Notification No. 0723-6). https:\/\/www.pmda.go.jp\/files\/000225191.pdf, English version:https:\/\/www.pmda.go.jp\/files\/000228122.pdf"},{"key":"4855_CR21","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/sj.clpt.6100187","volume":"82","author":"JY Ryu","year":"2007","unstructured":"Ryu JY, Song IS, Sunwoo YE, Shon JH, Liu KH, Cha IJ, Shin JG (2007) Development of the Inje cocktail for high-throughput evaluation of five human cytochrome P450 isoforms in vivo. Clin Pharmacol Ther 82:531\u2013540. https:\/\/doi.org\/10.1038\/sj.clpt.6100187","journal-title":"Clin Pharmacol Ther"}],"container-title":["Cancer Chemotherapy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00280-025-04855-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00280-025-04855-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00280-025-04855-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T03:27:25Z","timestamp":1769052445000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00280-025-04855-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4855"],"URL":"https:\/\/doi.org\/10.1007\/s00280-025-04855-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7677215\/v1","asserted-by":"object"}]},"ISSN":["1432-0843"],"issn-type":[{"value":"1432-0843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]},"assertion":[{"value":"22 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"N Yamamoto has received research grants as principal investigator (in institutional capacity) from Astellas Pharma, Chugai, Eisai, Taiho Pharmaceutical, Bristol-Myers Squibb, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa Kirin, Takeda, Ono Pharmaceutical, Janssen Pharma, MSD, MERCK, GSK, Chiome Bioscience, Otsuka Pharmaceutical, Carna Biosciences, Genmab, Shionogi, TORAY, KAKEN, AstraZeneca, InventisBio, Rakuten Medical, Amgen, Bicycle Therapeutics, and Zymeworks. N Yamamoto has received consulting fees (in personal capacity) from Eisai, Boehringer Ingelheim, Cmic, Chugai, MERCK, Healios, Mitsubishi Tanabe, Rakuten Medical, IQVIA, Noile-Immune Biotech, and Janssen Pharma. N Yamamoto has received payments for lectures (in personal capacity) from Chugai, Daiichi-Sankyo, and Eisai. Y Katsuya has received support for traveling to meetings not for the current study, but for another study from Ono Pharmaceutical. S Takenaka and S Takahashi declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14"}}