Division of Pediatric Hematology-Oncology, Moores Cancer Center, University of California, San Diego, CA 92093-0815, USA.
Trends Pharmacol Sci. 2024 Oct;45(10):904-918. doi: 10.1016/j.tips.2024.08.006. Epub 2024 Sep 24.
Spleen tyrosine kinase (SYK) is predominantly expressed in hematopoietic cells and has been extensively studied for its pivotal role in B cell malignancies and autoimmune diseases. In epithelial solid tumors, SYK shows a paradoxical role, acting as a tumor suppressor in some cancers while driving tumor growth in others. Recent preclinical studies have identified the role of SYK in the tumor microenvironment (TME), revealing that SYK signaling in immune cells, especially B cells, and myeloid cells, promote immunosuppression, tumor growth, and metastasis across various solid tumors. This review explores the emerging roles of SYK in solid tumors, the mechanisms of SYK activation, and findings from preclinical and clinical studies of SYK inhibitors as either standalone treatments or in combination with immunotherapy or chemotherapy for solid tumors.
脾酪氨酸激酶（SYK）主要在造血细胞中表达，因其在 B 细胞恶性肿瘤和自身免疫性疾病中的关键作用而得到广泛研究。在上皮性实体肿瘤中，SYK 表现出一种矛盾的作用，在一些癌症中作为肿瘤抑制因子，而在另一些癌症中则促进肿瘤生长。最近的临床前研究已经确定了 SYK 在肿瘤微环境（TME）中的作用，揭示了免疫细胞（尤其是 B 细胞和髓样细胞）中的 SYK 信号转导促进了各种实体肿瘤的免疫抑制、肿瘤生长和转移。这篇综述探讨了 SYK 在实体肿瘤中的新作用、SYK 激活的机制，以及临床前和临床研究中 SYK 抑制剂作为单一疗法或与免疫疗法或化疗联合治疗实体瘤的发现。
