文章：

靶向布鲁顿酪氨酸激酶治疗B细胞恶性肿瘤

Targeting Bruton's tyrosine kinase in B cell malignancies

原文发布日期：2014-03-24

DOI: 10.1038/nrc3702

类型: Review Article

开放获取: 否

要点：

1. Bruton's tyrosine kinase (BTK) was originally identified as a non-receptor protein tyrosine kinase that is defective in the inherited immunodeficiency disease X-linked agammaglobulinaemia (XLA).
2. BTK has long been known to be a key component of B cell receptor (BCR) signalling that regulates B cell proliferation and survival.
3. Recently, a small-molecule inhibitor of BTK, called ibrutinib, has shown antitumour activity in patients with various B cell malignancies.
4. The antitumour activity of BTK inhibition is not solely dependent on the role of BTK in BCR signalling.
5. BTK inhibition also targets Toll-like receptor (TLR) signalling, B cell adhesion and migration, as well as cells in the tumour microenvironment.
6. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukaemia and mantle cell lymphoma leads to the effective expulsion of malignant B cells out of their nursing microenvironment.
7. For many different B cell malignancies, treatment with BTK inhibitors is expected to be more effective and have fewer toxic effects than currently used therapies.

要点翻译：

1. 布鲁顿酪氨酸激酶（BTK）最初被鉴定为一种非受体蛋白酪氨酸激酶，其在遗传性免疫缺陷病X连锁无丙种球蛋白血症（XLA）中存在缺陷。
2. 长期以来，BTK已知是B细胞受体（BCR）信号传导的关键组成部分，调节B细胞的增殖和存活。
3. 最近，一种名为伊布替尼的小分子BTK抑制剂在多种B细胞恶性肿瘤患者中显示出抗肿瘤活性。
4. BTK抑制的抗肿瘤活性不仅依赖于BTK在BCR信号传导中的作用。
5. BTK抑制还靶向Toll样受体（TLR）信号传导、B细胞粘附和迁移，以及肿瘤微环境中的细胞。
6. 伊布替尼在慢性淋巴细胞白血病和套细胞淋巴瘤患者中诱导的淋巴细胞增多，导致恶性B细胞从其滋养微环境中有效排出。
7. 对于许多不同的B细胞恶性肿瘤，与目前使用的疗法相比，BTK抑制剂治疗预计更有效且毒性更小。

英文摘要：

Bruton's tyrosine kinase (BTK) is a key component of B cell receptor (BCR) signalling and functions as an important regulator of cell proliferation and cell survival in various B cell malignancies. Small-molecule inhibitors of BTK have shown antitumour activity in animal models and, recently, in clinical studies. High response rates were reported in patients with chronic lymphocytic leukaemia and mantle cell lymphoma. Remarkably, BTK inhibitors have molecular effects that cannot be explained by the classic role of BTK in BCR signalling. In this Review, we highlight the importance of BTK in various signalling pathways in the context of its therapeutic inhibition.

摘要翻译： 

布鲁顿酪氨酸激酶（BTK）是B细胞受体（BCR）信号通路的关键组分，在多种B细胞恶性肿瘤中作为细胞增殖和存活的重要调节因子。小分子BTK抑制剂在动物模型及近期临床研究中均显示出抗肿瘤活性，报道显示其对慢性淋巴细胞白血病和套细胞淋巴瘤患者具有较高缓解率。值得注意的是，BTK抑制剂产生的分子效应已超出BTK在BCR信号传导中的经典作用范畴。本文综述重点阐述BTK在不同信号通路中的重要性，并探讨其治疗性抑制的临床意义。

原文链接：

Targeting Bruton's tyrosine kinase in B cell malignancies