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Although treatment with ibrutinib has significantly improved the outcome of MCL patients, approximately one\u2010third of the patients have primary drug resistance while others appear to develop acquired resistance. Understanding the molecular events leading to the primary and acquired resistance to ibrutinib is essential for achieving better outcomes in patients with MCL. In this review, we describe the biology of the BCR signalling pathway and summarize the landmark clinical trials that have led to the approval of ibrutinib. We review the molecular mechanisms underlying primary and acquired ibrutinib resistance as well as recent studies dealing with overcoming ibrutinib resistance.<\/jats:p>","DOI":"10.1111\/bjh.15108","type":"journal-article","created":{"date-parts":[[2018,1,23]],"date-time":"2018-01-23T12:26:57Z","timestamp":1516710417000},"page":"306-319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Ibrutinib resistance in mantle cell lymphoma: clinical, molecular and treatment aspects"],"prefix":"10.1111","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4685-0679","authenticated-orcid":false,"given":"Oshrat","family":"Hershkovitz\u2010Rokah","sequence":"first","affiliation":[{"name":"Department of Molecular Biology Faculty of Natural Sciences Ariel University Ariel Israel"},{"name":"Translational Research Laboratory Assuta Medical Centres Tel Aviv Israel"},{"name":"Institute of Haematology Assuta Medical 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