{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:46:20Z","timestamp":1760453180492,"version":"3.40.5"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite significant efficacy of ibrutinib therapy in mantle cell lymphoma (MCL), about one\u2010third of MCL patients will display primary resistance. In time, secondary resistance occurs almost universally with an unlikely response to salvage chemotherapy afterwards. While intense efforts are being directed towards the characterization of resistance mechanisms, our focus is on identifying the signalling network rewiring that characterizes this ibrutinib resistant phenotype. Importantly, intrinsic genetic, epigenetic and tumour microenvironment\u2010initiated mechanisms have all been shown to influence the occurrence of the ibrutinib resistant phenotype. By using in vitro and in vivo models of primary and secondary ibrutinib resistance as well as post\u2010ibrutinib treatment clinical samples, we show that dual targeting of the BCL\u20102 and PI3\u2010kinase signalling pathways results in synergistic anti\u2010tumour activity. Clinically relevant doses of venetoclax, a BCL\u20102 inhibitor, in combination with duvelisib, a PI3K\u03b4\/\u03b3 dual inhibitor, resulted in significant inhibition of these compensatory pathways and apoptosis induction. Our preclinical results suggest that the combination of venetoclax and duvelisib may be a therapeutic option for MCL patients who experienced ibrutinib failure and merits careful consideration for future clinical trial evaluation.<\/jats:p>","DOI":"10.1111\/jcmm.17297","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T08:13:53Z","timestamp":1648628033000},"page":"3068-3073","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dual targeting of PI3K and BCL\u20102 overcomes ibrutinib resistance in aggressive mantle cell lymphoma"],"prefix":"10.1111","volume":"26","author":[{"given":"Haige","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Lymphoma and Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengjian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Lymphoma and Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Lymphoma and Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Lymphoma and Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Lymphoma and Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"},{"name":"Department of Stem Cell Transplantation and Cellular Therapy The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3778-4438","authenticated-orcid":false,"given":"Vivian Changying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Lymphoma and Myeloma The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V128.22.3016.3016"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1513257"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.4320"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.155"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13149"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14920"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.382"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-18-0478"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-1087"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-626846"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-272211"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2018-3459"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1730-1"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-0098"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V124.21.3334.3334"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2017.16"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2522"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph12020069"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3652"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0838-6"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.31.19236"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.17297","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.17297","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.17297","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T04:01:29Z","timestamp":1692504089000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.17297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,30]]},"references-count":21,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1111\/jcmm.17297"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.17297","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"type":"print","value":"1582-1838"},{"type":"electronic","value":"1582-4934"}],"subject":[],"published":{"date-parts":[[2022,3,30]]},"assertion":[{"value":"2021-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}