School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA.
Department of Endocrinology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, PR China.
Semin Cancer Biol. 2019 Jun;56:37-46. doi: 10.1016/j.semcancer.2017.10.002. Epub 2017 Oct 6.
Eph receptors and their Eph receptor-interacting (ephrin) ligands together form an important cell communication system with diverse roles. Experimental evidence demonstrated Eph receptor bidirectional signaling with both tumor-suppressing and tumor-promoting activities in cancer cells. The tyrosine kinase EphB4, a member of the Eph receptor family, has been associated with tumor angiogenesis, growth and metastasis, thus making it a valuable and attractive target for drug design for therapeutic applications. In the past decade, many studies have focused on elucidating the structure and function of EphB4 in complex with its ligand ephrinB2 for their role in carcinogenesis. Meanwhile, an array of compounds targeting EphB4 have been studied and several selective inhibitors have been tested in clinical studies. This review discusses the structure and function of the EphB4 receptor, analyzes its potential as a target for anticancer therapy, and summarizes the information about inhibitors of EphB4 kinase activity. Conclusively, EphB4 is a challenging but promising therapeutic target in cancer.
Eph 受体及其 Eph 受体相互作用（ephrin）配体共同构成了一个具有多种功能的重要细胞通讯系统。实验证据表明，Eph 受体在癌细胞中具有双向信号传递作用，既有肿瘤抑制作用，也有肿瘤促进作用。Eph 受体家族的成员酪氨酸激酶 EphB4 与肿瘤血管生成、生长和转移有关，因此成为药物设计治疗应用的有价值和有吸引力的靶点。在过去的十年中，许多研究集中在阐明 EphB4 与其配体 EphrinB2 形成复合物的结构和功能，以了解它们在致癌作用中的作用。同时，已经研究了一系列针对 EphB4 的化合物，并在临床研究中测试了几种选择性抑制剂。本文综述了 EphB4 受体的结构和功能，分析了其作为抗癌治疗靶点的潜力，并总结了 EphB4 激酶活性抑制剂的信息。总之，EphB4 是癌症治疗中具有挑战性但有前途的治疗靶点。
