Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel, Israel.
Translational Research Laboratory, Assuta Medical Centres, Tel Aviv, Israel.
Br J Haematol. 2018 May;181(3):306-319. doi: 10.1111/bjh.15108. Epub 2018 Jan 23.
Mantle cell lymphoma (MCL) is a lymphoproliferative disorder comprising about 6-10% of all B cell lymphoma cases. Ibrutinib is an inhibitor of Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. Although treatment with ibrutinib has significantly improved the outcome of MCL patients, approximately one-third 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.
套细胞淋巴瘤（MCL）是一种淋巴增生性疾病，约占所有 B 细胞淋巴瘤病例的 6-10%。依鲁替尼是布鲁顿酪氨酸激酶（BTK）的抑制剂，BTK 是早期 B 细胞受体（BCR）信号通路的关键组成部分。尽管依鲁替尼的治疗显著改善了 MCL 患者的预后，但约三分之一的患者存在原发性药物耐药，而其他患者似乎出现获得性耐药。了解导致依鲁替尼原发性和获得性耐药的分子事件对于改善 MCL 患者的预后至关重要。在这篇综述中，我们描述了 BCR 信号通路的生物学，并总结了导致依鲁替尼获批的里程碑式临床试验。我们回顾了原发性和获得性依鲁替尼耐药的分子机制，以及最近关于克服依鲁替尼耐药性的研究。
