Division of Pediatric Hematology-Oncology, First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Int J Mol Sci. 2024 Mar 29;25(7):3834. doi: 10.3390/ijms25073834.
Pediatric neoplasms represent a complex group of malignancies that pose unique challenges in terms of diagnosis, treatment, and understanding of the underlying molecular pathogenetic mechanisms. Erythropoietin-producing hepatocellular receptors (EPHs), the largest family of receptor tyrosine kinases and their membrane-tethered ligands, ephrins, orchestrate short-distance cell-cell signaling and are intricately involved in cell-pattern morphogenesis and various developmental processes. Unraveling the role of the EPH/ephrin signaling pathway in the pathophysiology of pediatric neoplasms and its clinical implications can contribute to deciphering the intricate landscape of these malignancies. The bidirectional nature of the EPH/ephrin axis is underscored by emerging evidence revealing its capacity to drive tumorigenesis, fostering cell-cell communication within the tumor microenvironment. In the context of carcinogenesis, the EPH/ephrin signaling pathway prompts a reevaluation of treatment strategies, particularly in pediatric oncology, where the modest progress in survival rates and enduring treatment toxicity necessitate novel approaches. Molecularly targeted agents have emerged as promising alternatives, prompting a shift in focus. Through a nuanced understanding of the pathway's intricacies, we aim to lay the groundwork for personalized diagnostic and therapeutic strategies, ultimately contributing to improved outcomes for young patients grappling with neoplastic challenges.
小儿肿瘤是一组复杂的恶性肿瘤,在诊断、治疗和对潜在分子发病机制的理解方面都存在独特的挑战。促红细胞生成素产生肝细胞受体(EPHs)是受体酪氨酸激酶家族中最大的家族,及其膜结合配体——ephrins,协调短距离细胞间信号传递,并深入参与细胞模式形态发生和各种发育过程。阐明 EPH/ephrin 信号通路在小儿肿瘤病理生理学中的作用及其临床意义,有助于揭示这些恶性肿瘤的复杂特征。EPH/ephrin 轴的双向性质由新出现的证据所强调,这些证据揭示了其驱动肿瘤发生的能力,并促进肿瘤微环境内的细胞间通讯。在致癌作用方面,EPH/ephrin 信号通路促使人们重新评估治疗策略,特别是在儿科肿瘤学中,生存率的适度提高和持续的治疗毒性需要新的方法。分子靶向药物已成为有前途的替代品,促使人们的关注点发生转移。通过对该通路复杂性的细致理解,我们旨在为个性化诊断和治疗策略奠定基础,最终为应对肿瘤挑战的年轻患者带来更好的结果。