Department of Molecular Genetics, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada.
Mol Biol Rep. 2020 Jul;47(7):5523-5533. doi: 10.1007/s11033-020-05571-8. Epub 2020 Jul 3.
The erythropoietin-producing human hepatocellular (Eph) receptors are transmembrane glycoprotein members of the tyrosine kinase receptors family. The Ephs may bind to various ephrin ligands resulting in the phosphorylation of their tyrosine kinase domain and the activation of the Eph receptor. In this review we focus on EphA3, one receptor of the 14 different Ephs, as it carries out both redundant and restricted functions in the germline development of mammals and in the maintenance of various adult tissues. The loss of EphA3 regulation is correlated with various human malignancies, the most notable being cancer. This receptor is overexpressed and/or mutated in multiple tumors, and is also associated with poor prognosis and decreased survival in patients. Here we highlight the role of EphA3 in normal and malignant tissues that are specific to cancer; these include hematologic disorders, gastric cancer, glioblastoma multiforme, colorectal cancer, lung cancer, renal cell carcinoma, and prostate cancer. Moreover, various anticancer agents against EphA3 have been developed to either inhibit its kinase domain activity or to function as agonists. Thus, we examine the most potent small molecule drugs and mAb-based therapeutics against EphA3 that are currently in pre-clinical or clinical stages.
促红细胞生成素产生的人肝细胞 (Eph) 受体是酪氨酸激酶受体家族的跨膜糖蛋白成员。Eph 可能与各种 Ephrin 配体结合，导致其酪氨酸激酶结构域磷酸化，并激活 Eph 受体。在这篇综述中，我们重点介绍 EphA3，这是 14 种不同 Eph 中的一种受体，因为它在哺乳动物的生殖系发育和各种成人组织的维持中发挥着冗余和受限的功能。EphA3 调节的丧失与各种人类恶性肿瘤相关，最显著的是癌症。该受体在多种肿瘤中过度表达和/或突变，并且与患者预后不良和生存率降低相关。在这里，我们强调 EphA3 在特定于癌症的正常和恶性组织中的作用；这些包括血液系统疾病、胃癌、胶质母细胞瘤、结直肠癌、肺癌、肾细胞癌和前列腺癌。此外，已经开发了各种针对 EphA3 的抗癌剂，以抑制其激酶结构域活性或作为激动剂发挥作用。因此，我们研究了目前处于临床前或临床阶段的针对 EphA3 的最有效小分子药物和基于 mAb 的治疗方法。
