Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Rev Cancer. 2018 Mar;18(3):148-167. doi: 10.1038/nrc.2017.121. Epub 2018 Jan 19.
B cell receptor (BCR) signalling is crucial for normal B cell development and adaptive immunity. BCR signalling also supports the survival and growth of malignant B cells in patients with B cell leukaemias or lymphomas. The mechanism of BCR pathway activation in these diseases includes continuous BCR stimulation by microbial antigens or autoantigens present in the tissue microenvironment, activating mutations within the BCR complex or downstream signalling components and ligand-independent tonic BCR signalling. The most established agents targeting BCR signalling are Bruton tyrosine kinase (BTK) inhibitors and PI3K isoform-specific inhibitors, and their introduction into the clinic is rapidly changing how B cell malignancies are treated. B cells and BCR-related kinases, such as BTK, also play a role in the microenvironment of solid tumours, such as squamous cell carcinoma and pancreatic cancer, and therefore targeting B cells or BCR-related kinases may have anticancer activity beyond B cell malignancies.
B 细胞受体 (BCR) 信号转导对于正常 B 细胞发育和适应性免疫至关重要。BCR 信号转导还支持患有 B 细胞白血病或淋巴瘤的患者中恶性 B 细胞的存活和生长。这些疾病中 BCR 途径激活的机制包括微生物抗原或组织微环境中存在的自身抗原持续刺激 BCR，BCR 复合物或下游信号转导成分内的激活突变，以及配体非依赖性持续 BCR 信号转导。针对 BCR 信号转导的最成熟的药物是布鲁顿酪氨酸激酶 (BTK) 抑制剂和 PI3K 同工型特异性抑制剂，它们在临床上的应用正在迅速改变 B 细胞恶性肿瘤的治疗方法。B 细胞和 BCR 相关激酶（如 BTK）也在鳞状细胞癌和胰腺癌等实体瘤的微环境中发挥作用，因此，针对 B 细胞或 BCR 相关激酶可能具有超越 B 细胞恶性肿瘤的抗癌活性。
