Lodola Alessio, Giorgio Carmine, Incerti Matteo, Zanotti Ilaria, Tognolini Massimiliano
Department of Food and Drug, University of Parma, Viale delle Scienze 27/a, 43124 Parma, Italy.
Department of Food and Drug, University of Parma, Viale delle Scienze 27/a, 43124 Parma, Italy.
Eur J Med Chem. 2017 Dec 15;142:152-162. doi: 10.1016/j.ejmech.2017.07.029. Epub 2017 Jul 18.
It is well established that the Eph/ephrin system plays a central role in the embryonic development, with minor implications in the physiology of the adult. However, it is overexpressed and deregulated in a variety of tumors, with a primary involvement in tumorigenesis, tumor angiogenesis, metastasis development, and cancer stem cell regeneration. Targeting the Eph/ephrin system with biologicals, including antibodies and recombinant proteins, reduces tumor growth in animal models of hematological malignancies, breast, prostate, colon, head and neck cancers and glioblastoma. Currently, some of these biopharmaceutical agents are under investigations in phase I or phase II clinical trials. Peptides and small molecules targeting protein-protein-interaction (PPI) are in the late preclinical phase where they are showing promising activity in models of glioblastoma, ovarian and lung cancer. The present review summarizes the most critical findings proposing the Eph/ephrin signaling system as a new target in molecularly targeted oncology.
Eph/ephrin系统在胚胎发育中起核心作用，而在成人生理学中的影响较小，这一点已得到充分证实。然而，它在多种肿瘤中过度表达且失调，主要参与肿瘤发生、肿瘤血管生成、转移发展和癌症干细胞再生。使用包括抗体和重组蛋白在内的生物制剂靶向Eph/ephrin系统，可减少血液系统恶性肿瘤、乳腺癌、前列腺癌、结肠癌、头颈癌和胶质母细胞瘤动物模型中的肿瘤生长。目前，其中一些生物制药制剂正处于I期或II期临床试验阶段。靶向蛋白质-蛋白质相互作用（PPI）的肽和小分子正处于临床前后期阶段，在胶质母细胞瘤、卵巢癌和肺癌模型中显示出有前景的活性。本综述总结了最关键的研究结果，提出Eph/ephrin信号系统作为分子靶向肿瘤学中的一个新靶点。
