{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:46:21Z","timestamp":1790552781876,"version":"4.1.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,1,4]],"date-time":"2020-01-04T00:00:00Z","timestamp":1578096000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,1,4]],"date-time":"2020-01-04T00:00:00Z","timestamp":1578096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1007\/s00280-019-04022-x","type":"journal-article","created":{"date-parts":[[2020,1,4]],"date-time":"2020-01-04T17:02:36Z","timestamp":1578157356000},"page":"401-412","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effect of dual inhibition of histone deacetylase and phosphatidylinositol-3 kinase in Philadelphia chromosome-positive leukemia cells"],"prefix":"10.1007","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2727-658X","authenticated-orcid":false,"given":"Seiichi","family":"Okabe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Moriyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Gotoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,4]]},"reference":[{"key":"4022_CR1","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/243290a0","volume":"243","author":"JD Rowley","year":"1973","unstructured":"Rowley JD (1973) Letter: a new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:290\u2013293. https:\/\/doi.org\/10.1038\/243290a0","journal-title":"Nature"},{"key":"4022_CR2","doi-asserted-by":"publisher","first-page":"913","DOI":"10.7326\/0003-4819-145-12-200612190-00008","volume":"145","author":"HM Kantarjian","year":"2006","unstructured":"Kantarjian HM, Talpaz M, Giles F, O\u2019Brien S, Cortes J (2006) New insights into the pathophysiology of chronic myeloid leukemia and imatinib resistance. Ann Intern Med 145:913\u2013923. https:\/\/doi.org\/10.7326\/0003-4819-145-12-200612190-00008","journal-title":"Ann Intern Med"},{"key":"4022_CR3","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1056\/NEJMoa011573","volume":"346","author":"H Kantarjian","year":"2002","unstructured":"Kantarjian H, Sawyers C, Hochhaus A et al (2002) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346:645\u2013652. https:\/\/doi.org\/10.1056\/NEJMoa011573","journal-title":"N Engl J Med"},{"key":"4022_CR4","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1056\/NEJMoa0912614","volume":"362","author":"G Saglio","year":"2010","unstructured":"Saglio G, Kim DW, Issaragrisil S et al (2010) Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 362:2251\u20132259. https:\/\/doi.org\/10.1056\/NEJMoa0912614","journal-title":"N Engl J Med"},{"key":"4022_CR5","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1056\/NEJMoa1002315","volume":"362","author":"H Kantarjian","year":"2010","unstructured":"Kantarjian H, Shah NP, Hochhaus A, Cortes J et al (2010) Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 362:2260\u20132270. https:\/\/doi.org\/10.1056\/NEJMoa1002315","journal-title":"N Engl J Med"},{"key":"4022_CR6","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/nrd2324","volume":"6","author":"A Quint\u00e1s-Cardama","year":"2007","unstructured":"Quint\u00e1s-Cardama A, Kantarjian H, Cortes J (2007) Flying under the radar: the new wave of BCR-ABL inhibitors. Nat Rev Drug Discov 6:834\u2013848. https:\/\/doi.org\/10.1038\/nrd2324","journal-title":"Nat Rev Drug Discov"},{"key":"4022_CR7","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.1080\/10428190701665988","volume":"48","author":"L Kujawski","year":"2007","unstructured":"Kujawski L, Talpaz M (2007) Strategies for overcoming imatinib resistance in chronic myeloid leukemia. Leuk Lymphoma 48:2310\u20132322. https:\/\/doi.org\/10.1080\/10428190701665988","journal-title":"Leuk Lymphoma"},{"key":"4022_CR8","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1172\/JCI35721","volume":"121","author":"AS Corbin","year":"2011","unstructured":"Corbin AS, Agarwal A, Loriaux M, Cortes J, Deininger MW, Druker BJ (2011) Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest 121:396\u2013409. https:\/\/doi.org\/10.1172\/JCI35721","journal-title":"J Clin Invest"},{"key":"4022_CR9","doi-asserted-by":"publisher","first-page":"89","DOI":"10.18632\/oncotarget.114","volume":"1","author":"AM Martelli","year":"2010","unstructured":"Martelli AM, Evangelisti C, Chiarini F, McCubrey JA (2010) The phosphatidylinositol 3-kinase\/Akt\/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients. Oncotarget 1:89\u2013103. https:\/\/doi.org\/10.18632\/oncotarget.114","journal-title":"Oncotarget"},{"key":"4022_CR10","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1111\/bph.12183","volume":"169","author":"A Sinclair","year":"2013","unstructured":"Sinclair A, Latif AL, Holyoake TL (2013) Targeting survival pathways in chronic myeloid leukaemia stem cells. Br J Pharmacol 169:1693\u20131707. https:\/\/doi.org\/10.1111\/bph.12183","journal-title":"Br J Pharmacol"},{"key":"4022_CR11","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/nrclinonc.2018.28","volume":"15","author":"F Janku","year":"2018","unstructured":"Janku F, Yap TA, Meric-Bernstam F (2018) Targeting the PI3K pathway in cancer: are we making headway? Nat Rev Clin Oncol 15:273\u2013291. https:\/\/doi.org\/10.1038\/nrclinonc.2018.28","journal-title":"Nat Rev Clin Oncol"},{"key":"4022_CR12","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1586\/14789450.2.5.719","volume":"2","author":"L Mari\u00f1o-Ram\u00edrez","year":"2005","unstructured":"Mari\u00f1o-Ram\u00edrez L, Kann MG, Shoemaker BA, Landsman D (2005) Histone structure and nucleosome stability. Expert Rev Proteomics 2:719\u2013729. https:\/\/doi.org\/10.1586\/14789450.2.5.719","journal-title":"Expert Rev Proteomics"},{"key":"4022_CR13","doi-asserted-by":"publisher","first-page":"89315","DOI":"10.18632\/oncotarget.19167","volume":"8","author":"N Liu","year":"2017","unstructured":"Liu N, Li S, Wu N, Cho KS (2017) Acetylation and deacetylation in cancer stem-like cells. Oncotarget 8:89315\u201389325. https:\/\/doi.org\/10.18632\/oncotarget.19167","journal-title":"Oncotarget"},{"key":"4022_CR14","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s13045-017-0463-6","volume":"10","author":"C Saygin","year":"2017","unstructured":"Saygin C, Carraway HE (2017) Emerging therapies for acute myeloid leukemia. J Hematol Oncol 10:93. https:\/\/doi.org\/10.1186\/s13045-017-0463-6","journal-title":"J Hematol Oncol"},{"key":"4022_CR15","doi-asserted-by":"publisher","DOI":"10.1002\/med.21600","author":"D Tomaselli","year":"2019","unstructured":"Tomaselli D, Lucidi A, Rotili D, Mai A (2019) Epigenetic polypharmacology: a new frontier for epi-drug discovery. Med Res Rev. https:\/\/doi.org\/10.1002\/med.21600","journal-title":"Med Res Rev"},{"key":"4022_CR16","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1756-8722-4-32","volume":"4","author":"S Okabe","year":"2011","unstructured":"Okabe S, Tauchi T, Tanaka Y, Ohyashiki K (2011) Dasatinib preferentially induces apoptosis by inhibiting Lyn kinase in nilotinib-resistant chronic myeloid leukemia cell line. J Hematol Oncol 4:32. https:\/\/doi.org\/10.1186\/1756-8722-4-32","journal-title":"J Hematol Oncol"},{"key":"4022_CR17","doi-asserted-by":"publisher","first-page":"3086","DOI":"10.1182\/blood-2013-04-494773","volume":"122","author":"S Okabe","year":"2013","unstructured":"Okabe S, Tauchi T, Tanaka Y, Katagiri S, Kitahara T, Ohyashiki K (2013) Activity of omacetaxine mepesuccinate against ponatinib-resistant BCR-ABL-positive cells. Blood 122:3086\u20133088. https:\/\/doi.org\/10.1182\/blood-2013-04-494773","journal-title":"Blood"},{"key":"4022_CR18","doi-asserted-by":"publisher","first-page":"3948","DOI":"10.1182\/blood-2005-06-2209","volume":"106","author":"S Kimura","year":"2005","unstructured":"Kimura S, Naito H, Segawa H et al (2005) NS\u2212187, a potent and selective dual Bcr-Abl\/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia. Blood 106:3948\u20133954. https:\/\/doi.org\/10.1182\/blood-2005-06-2209","journal-title":"Blood"},{"issue":"2","key":"4022_CR19","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","volume":"70","author":"TC Chou","year":"2010","unstructured":"Chou TC (2010) (2010) Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70(2):440\u2013446. https:\/\/doi.org\/10.1158\/0008-5472.CAN-09-1947","journal-title":"Cancer Res."},{"key":"4022_CR20","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s00277-018-3547-7","volume":"98","author":"S Okabe","year":"2019","unstructured":"Okabe S, Tanaka Y, Tauchi T, Ohyashiki K (2019) Copanlisib, a novel phosphoinositide 3-kinase inhibitor, combined with carfilzomib inhibits multiple myeloma cell proliferation. Ann Hematol 98:723\u2013733. https:\/\/doi.org\/10.1007\/s00277-018-3547-7","journal-title":"Ann Hematol"},{"key":"4022_CR21","doi-asserted-by":"publisher","first-page":"32496","DOI":"10.18632\/oncotarget.25985","volume":"9","author":"S Okabe","year":"2018","unstructured":"Okabe S, Tauchi T, Tanaka Y, Ohyashiki K (2018) Therapeutic targeting of aurora A kinase in Philadelphia chromosome-positive ABL tyrosine kinase inhibitor-resistant cells. Oncotarget 9:32496\u201332506. https:\/\/doi.org\/10.18632\/oncotarget.25985","journal-title":"Oncotarget"},{"key":"4022_CR22","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.3390\/ijms20092271","volume":"20","author":"SH Chen","year":"2019","unstructured":"Chen SH, Chow JM, Hsieh YY et al (2019) HDAC1,2 knock-out and HDACi induced cell apoptosis in imatinib-resistant K562 cells. Int J Mol Sci 20:2271. https:\/\/doi.org\/10.3390\/ijms20092271","journal-title":"Int J Mol Sci"},{"key":"4022_CR23","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.ccr.2009.09.028","volume":"16","author":"T O\u2019Hare","year":"2009","unstructured":"O\u2019Hare T, Shakespeare WC, Zhu X et al (2009) AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 16:401\u2013412. https:\/\/doi.org\/10.1016\/j.ccr.2009.09.028","journal-title":"Cancer Cell"},{"key":"4022_CR24","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.3324\/haematol.2017.172882","volume":"102","author":"Y Oki","year":"2017","unstructured":"Oki Y, Kelly KR, Flinn I, Patel MR, Gharavi R, Ma A, Parker J, Hafeez A, Tuck D, Younes A (2017) CUDC-907 in relapsed\/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial. Haematologica 102:1923\u20131930. https:\/\/doi.org\/10.3324\/haematol.2017.172882","journal-title":"Haematologica"},{"key":"4022_CR25","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/S1470-2045(15)00584-7","volume":"17","author":"A Younes","year":"2016","unstructured":"Younes A, Berdeja JG, Patel MR et al (2016) Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial. Lancet Oncol 17:622\u2013631. https:\/\/doi.org\/10.1016\/S1470-2045(15)00584-7","journal-title":"Lancet Oncol"},{"key":"4022_CR26","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1038\/s41388-018-0550-3","volume":"38","author":"H Guo","year":"2019","unstructured":"Guo H, Zeng D, Zhang H et al (2019) Dual inhibition of PI3K signaling and histone deacetylation halts proliferation and induces lethality in mantle cell lymphoma. Oncogene 38:1802\u20131814. https:\/\/doi.org\/10.1038\/s41388-018-0550-3","journal-title":"Oncogene"},{"key":"4022_CR27","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/jcmm.13935","volume":"23","author":"Y Chen","year":"2019","unstructured":"Chen Y, Peubez C, Smith V et al (2019) CUDC-907 blocks multiple pro-survival signals and abrogates microenvironment protection in CLL. J Cell Mol Med 23:340\u2013348. https:\/\/doi.org\/10.1111\/jcmm.13935","journal-title":"J Cell Mol Med"},{"key":"4022_CR28","doi-asserted-by":"publisher","first-page":"4007","DOI":"10.1158\/0008-5472.CAN-17-3691","volume":"78","author":"S Pal","year":"2018","unstructured":"Pal S, Kozono D, Yang X et al (2018) Dual HDAC and PI3K inhibition abrogates NF\u03baB- and FOXM1-mediated DNA damage response to radiosensitize pediatric high-grade gliomas. Cancer Res 78:4007\u20134021. https:\/\/doi.org\/10.1158\/0008-5472.CAN-17-3691","journal-title":"Cancer Res"},{"key":"4022_CR29","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.3324\/haematol.2018.201343","volume":"104","author":"X Li","year":"2019","unstructured":"Li X, Su Y, Madlambayan G et al (2019) Antileukemic activity and mechanism of action of the novel PI3K and histone deacetylase dual inhibitor CUDC-907 in acute myeloid leukemia. Haematologica 104:2225\u20132240. https:\/\/doi.org\/10.3324\/haematol.2018.201343","journal-title":"Haematologica"}],"container-title":["Cancer Chemotherapy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00280-019-04022-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00280-019-04022-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00280-019-04022-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T00:14:25Z","timestamp":1609632865000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00280-019-04022-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,4]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["4022"],"URL":"https:\/\/doi.org\/10.1007\/s00280-019-04022-x","relation":{},"ISSN":["0344-5704","1432-0843"],"issn-type":[{"value":"0344-5704","type":"print"},{"value":"1432-0843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,4]]},"assertion":[{"value":"29 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the local institute committee.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}