{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:38:26Z","timestamp":1773099506540,"version":"3.50.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T00:00:00Z","timestamp":1518480000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["MFAG14456"],"award-info":[{"award-number":["MFAG14456"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Targ Oncol"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1007\/s11523-018-0553-6","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T05:11:03Z","timestamp":1518498663000},"page":"235-245","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Combining Ibrutinib with Chk1 Inhibitors Synergistically Targets Mantle Cell Lymphoma Cell Lines"],"prefix":"10.1007","volume":"13","author":[{"given":"Valentina","family":"Restelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Lupi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micaela","family":"Vagni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosaria","family":"Chil\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Bertoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Damia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Carrassa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,2,13]]},"reference":[{"issue":"7","key":"553_CR1","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1080\/10428194.2016.1248965","volume":"58","author":"N Vogt","year":"2017","unstructured":"Vogt N, Dai B, Erdmann T, Berdel WE, Lenz G. The molecular pathogenesis of mantle cell lymphoma. Leuk Lymphoma. 2017;58(7):1530\u20137.","journal-title":"Leuk Lymphoma"},{"issue":"20","key":"553_CR2","first-page":"4608","volume":"57","author":"MH Dreyling","year":"1997","unstructured":"Dreyling MH, Bullinger L, Ott G, Stilgenbauer S, Muller-Hermelink HK, Bentz M, et al. Alterations of the cyclin D1\/p16-pRB pathway in mantle cell lymphoma. Cancer Res. 1997;57(20):4608\u201314.","journal-title":"Cancer Res"},{"issue":"8","key":"553_CR3","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.1182\/blood-2002-01-0263","volume":"101","author":"L Quintanilla-Martinez","year":"2003","unstructured":"Quintanilla-Martinez L, Davies-Hill T, Fend F, Calzada-Wack J, Sorbara L, Campo E, et al. Sequestration of p27Kip1 protein by cyclin D1 in typical and blastic variants of mantle cell lymphoma (MCL): implications for pathogenesis. Blood. 2003;101(8):3181\u20137.","journal-title":"Blood"},{"issue":"1","key":"553_CR4","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1182\/blood.V99.1.238","volume":"99","author":"E Camacho","year":"2002","unstructured":"Camacho E, Hernandez L, Hernandez S, Tort F, Bellosillo B, Bea S, et al. ATM gene inactivation in mantle cell lymphoma mainly occurs by truncating mutations and missense mutations involving the phosphatidylinositol-3 kinase domain and is associated with increasing numbers of chromosomal imbalances. Blood. 2002;99(1):238\u201344.","journal-title":"Blood"},{"issue":"12","key":"553_CR5","first-page":"4365","volume":"93","author":"S Bea","year":"1999","unstructured":"Bea S, Ribas M, Hernandez JM, Bosch F, Pinyol M, Hernandez L, et al. Increased number of chromosomal imbalances and high-level DNA amplifications in mantle cell lymphoma are associated with blastoid variants. Blood. 1999;93(12):4365\u201374.","journal-title":"Blood"},{"issue":"1","key":"553_CR6","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1182\/blood-2014-05-521898","volume":"125","author":"E Campo","year":"2015","unstructured":"Campo E, Rule S. Mantle cell lymphoma: evolving management strategies. Blood. 2015;125(1):48\u201355.","journal-title":"Blood"},{"issue":"1","key":"553_CR7","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1182\/blood-2015-11-681460","volume":"128","author":"NS Saba","year":"2016","unstructured":"Saba NS, Liu D, Herman SE, Underbayev C, Tian X, Behrend D, et al. Pathogenic role of B-cell receptor signaling and canonical NF-kappaB activation in mantle cell lymphoma. Blood. 2016;128(1):82\u201392.","journal-title":"Blood"},{"issue":"11","key":"553_CR8","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.3324\/haematol.2009.019745","volume":"95","author":"F Baran-Marszak","year":"2010","unstructured":"Baran-Marszak F, Boukhiar M, Harel S, Laguillier C, Roger C, Gressin R, et al. Constitutive and B-cell receptor-induced activation of STAT3 are important signaling pathways targeted by bortezomib in leukemic mantle cell lymphoma. Haematologica. 2010;95(11):1865\u201372.","journal-title":"Haematologica"},{"issue":"6","key":"553_CR9","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1056\/NEJMoa1306220","volume":"369","author":"ML Wang","year":"2013","unstructured":"Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369(6):507\u201316.","journal-title":"N Engl J Med"},{"issue":"4","key":"553_CR10","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1111\/bjh.13427","volume":"170","author":"SQ Zhang","year":"2015","unstructured":"Zhang SQ, Smith SM, Zhang SY, Lynn Wang Y. Mechanisms of ibrutinib resistance in chronic lymphocytic leukaemia and non-Hodgkin lymphoma. Br J Haematol. 2015;170(4):445\u201356.","journal-title":"Br J Haematol"},{"issue":"1","key":"553_CR11","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ccr.2013.12.011","volume":"25","author":"D Colomer","year":"2014","unstructured":"Colomer D, Campo E. Unlocking new therapeutic targets and resistance mechanisms in mantle cell lymphoma. Cancer Cell. 2014;25(1):7\u20139.","journal-title":"Cancer Cell"},{"issue":"9","key":"553_CR12","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1158\/2159-8290.CD-14-0098","volume":"4","author":"D Chiron","year":"2014","unstructured":"Chiron D, Di Liberto M, Martin P, Huang X, Sharman J, Blecua P, et al. Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma. Cancer Discov. 2014;4(9):1022\u201335.","journal-title":"Cancer Discov"},{"issue":"1","key":"553_CR13","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nm.3435","volume":"20","author":"R Rahal","year":"2014","unstructured":"Rahal R, Frick M, Romero R, Korn JM, Kridel R, Chan FC, et al. Pharmacological and genomic profiling identifies NF-kappaB-targeted treatment strategies for mantle cell lymphoma. Nat Med. 2014;20(1):87\u201392.","journal-title":"Nat Med"},{"issue":"5","key":"553_CR14","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.18632\/oncotarget.2583","volume":"6","author":"R Chila","year":"2015","unstructured":"Chila R, Basana A, Lupi M, Guffanti F, Gaudio E, Rinaldi A, et al. Combined inhibition of Chk1 and Wee1 as a new therapeutic strategy for mantle cell lymphoma. Oncotarget. 2015;6(5):3394\u2013408.","journal-title":"Oncotarget"},{"issue":"35","key":"553_CR15","doi-asserted-by":"publisher","first-page":"37229","DOI":"10.18632\/oncotarget.5954","volume":"6","author":"V Restelli","year":"2015","unstructured":"Restelli V, Chila R, Lupi M, Rinaldi A, Kwee I, Bertoni F, et al. Characterization of a mantle cell lymphoma cell line resistant to the Chk1 inhibitor PF-00477736. Oncotarget. 2015;6(35):37229\u201340.","journal-title":"Oncotarget"},{"issue":"13","key":"553_CR16","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.4161\/cc.20899","volume":"11","author":"L Carrassa","year":"2012","unstructured":"Carrassa L, Chila R, Lupi M, Ricci F, Celenza C, Mazzoletti M, et al. Combined inhibition of Chk1 and Wee1: in vitro synergistic effect translates to tumor growth inhibition in vivo. Cell Cycle. 2012;11(13):2507\u201317.","journal-title":"Cell Cycle"},{"issue":"8A","key":"553_CR17","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1111\/j.1582-4934.2008.00362.x","volume":"13","author":"L Carrassa","year":"2009","unstructured":"Carrassa L, Sanchez Y, Erba E, Damia G. U2OS cells lacking Chk1 undergo aberrant mitosis and fail to activate the spindle checkpoint. J Cell Mol Med. 2009;13(8A):1565\u201376.","journal-title":"J Cell Mol Med"},{"issue":"2-3","key":"553_CR18","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/0010-468X(85)90007-8","volume":"19","author":"P Ubezio","year":"1985","unstructured":"Ubezio P. Microcomputer experience in analysis of flow cytometric DNA distributions. Comput Programs Biomed. 1985;19(2-3):159\u201366.","journal-title":"Comput Programs Biomed"},{"issue":"29","key":"553_CR19","doi-asserted-by":"publisher","first-page":"13075","DOI":"10.1073\/pnas.1004594107","volume":"107","author":"LA Honigberg","year":"2010","unstructured":"Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010;107(29):13075\u201380.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"20","key":"553_CR20","doi-asserted-by":"publisher","first-page":"7529","DOI":"10.1128\/MCB.00447-06","volume":"26","author":"V Leung-Pineda","year":"2006","unstructured":"Leung-Pineda V, Ryan CE, Piwnica-Worms H. Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit. Mol Cell Biol. 2006;26(20):7529\u201338.","journal-title":"Mol Cell Biol"},{"issue":"6","key":"553_CR21","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/j.hoc.2016.07.014","volume":"30","author":"A Goy","year":"2016","unstructured":"Goy A. Mantle cell lymphoma: is it time for a new treatment paradigm? Hematol Oncol Clin North Am. 2016;30(6):1345\u201370.","journal-title":"Hematol Oncol Clin North Am"},{"issue":"30","key":"553_CR22","doi-asserted-by":"publisher","first-page":"48692","DOI":"10.18632\/oncotarget.8961","volume":"7","author":"AA Inamdar","year":"2016","unstructured":"Inamdar AA, Goy A, Ayoub NM, Attia C, Oton L, Taruvai V, et al. Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents. Oncotarget. 2016;7(30):48692\u2013731.","journal-title":"Oncotarget"},{"issue":"6","key":"553_CR23","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1080\/14737140.2017.1328280","volume":"17","author":"D Tucker","year":"2017","unstructured":"Tucker D, Rule S. Novel agents in mantle cell lymphoma. Expert Rev Anticancer Ther. 2017;17(6):491\u2013506.","journal-title":"Expert Rev Anticancer Ther"},{"issue":"6","key":"553_CR24","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1093\/annonc\/mdv111","volume":"26","author":"CY Cheah","year":"2015","unstructured":"Cheah CY, Chihara D, Romaguera JE, Fowler NH, Seymour JF, Hagemeister FB, et al. Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes. Ann Oncol. 2015;26(6):1175\u20139.","journal-title":"Ann Oncol"},{"issue":"12","key":"553_CR25","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1182\/blood-2015-10-673145","volume":"127","author":"P Martin","year":"2016","unstructured":"Martin P, Maddocks K, Leonard JP, Ruan J, Goy A, Wagner-Johnston N, et al. Postibrutinib outcomes in patients with mantle cell lymphoma. Blood. 2016;127(12):1559\u201363.","journal-title":"Blood"},{"issue":"1","key":"553_CR26","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s00280-014-2617-3","volume":"75","author":"E Marostica","year":"2015","unstructured":"Marostica E, Sukbuntherng J, Loury D, de Jong J, de Trixhe XW, Vermeulen A, et al. Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. Cancer Chemother Pharmacol. 2015;75(1):111\u201321.","journal-title":"Cancer Chemother Pharmacol"},{"issue":"6","key":"553_CR27","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1158\/1541-7786.MCR-05-0028","volume":"3","author":"SM Wuerzberger-Davis","year":"2005","unstructured":"Wuerzberger-Davis SM, Chang PY, Berchtold C, Miyamoto S. Enhanced G2-M arrest by nuclear factor-{kappa}B-dependent p21waf1\/cip1 induction. Mol Cancer Res. 2005;3(6):345\u201353.","journal-title":"Mol Cancer Res"},{"issue":"1","key":"553_CR28","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1475-2867-14-32","volume":"14","author":"X Zheng","year":"2014","unstructured":"Zheng X, Ding N, Song Y, Feng L, Zhu J. Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment. Cancer Cell Int. 2014;14(1):32.","journal-title":"Cancer Cell Int"},{"issue":"15","key":"553_CR29","doi-asserted-by":"publisher","first-page":"12710","DOI":"10.1074\/jbc.M111598200","volume":"277","author":"D Tang","year":"2002","unstructured":"Tang D, Wu D, Hirao A, Lahti JM, Liu L, Mazza B, et al. ERK activation mediates cell cycle arrest and apoptosis after DNA damage independently of p53. J Biol Chem. 2002;277(15):12710\u20137.","journal-title":"J Biol Chem"},{"issue":"1","key":"553_CR30","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1742-4658.2009.07366.x","volume":"277","author":"S Cagnol","year":"2010","unstructured":"Cagnol S, Chambard JC. ERK and cell death: mechanisms of ERK-induced cell death--apoptosis, autophagy and senescence. FEBS J. 2010;277(1):2\u201321.","journal-title":"FEBS J"},{"issue":"6","key":"553_CR31","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1038\/sj.emboj.7600608","volume":"24","author":"S Rocha","year":"2005","unstructured":"Rocha S, Garrett MD, Campbell KJ, Schumm K, Perkins ND. Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor. EMBO J. 2005;24(6):1157\u201369.","journal-title":"EMBO J"}],"container-title":["Targeted Oncology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11523-018-0553-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11523-018-0553-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11523-018-0553-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T20:23:27Z","timestamp":1550003007000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11523-018-0553-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,13]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["553"],"URL":"https:\/\/doi.org\/10.1007\/s11523-018-0553-6","relation":{},"ISSN":["1776-2596","1776-260X"],"issn-type":[{"value":"1776-2596","type":"print"},{"value":"1776-260X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,13]]},"assertion":[{"value":"13 February 2018","order":1,"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":"This work was supported by the Italian Association for Cancer Research (AIRC), Milan, Italy (MFAG14456 to Laura Carrassa), and partially supported by the Gelu Foundation (to Francesco Bertoni).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare no competing financial interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}