Broccoli Alessandro, Del Re Marzia, Danesi Romano, Zinzani Pier Luigi
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.
Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy.
J Cell Mol Med. 2025 Feb;29(3):e70170. doi: 10.1111/jcmm.70170.
Bruton tyrosine kinase (BTK), the primary target of BTK inhibitors, is a key enzyme in the proliferation and survival pathway of neoplastic B-cells. BTK inhibitors are approved in many hematologic malignancies: chronic lymphocytic leukaemia, mantle cell lymphoma, marginal zone lymphoma, Waldenström macroglobulinaemia and follicular lymphoma. Second-generation BTK inhibitors display high target selectivity thus resulting in a reduction in off-target and off-tissue effects, better therapeutic index and improved tolerability. This paper summarizes the mechanisms of action of first and second generation BTK inhibitors and elucidates results in any disease setting, with a precise focus on zanubrutinib.
布鲁顿酪氨酸激酶（BTK）是BTK抑制剂的主要靶点，是肿瘤性B细胞增殖和存活途径中的关键酶。BTK抑制剂已在多种血液系统恶性肿瘤中获批：慢性淋巴细胞白血病、套细胞淋巴瘤、边缘区淋巴瘤、华氏巨球蛋白血症和滤泡性淋巴瘤。第二代BTK抑制剂具有高靶点选择性，因此可减少脱靶和脱组织效应，具有更好的治疗指数和更高的耐受性。本文总结了第一代和第二代BTK抑制剂的作用机制，并阐述了在任何疾病背景下的结果，特别聚焦于泽布替尼。
