Zhang Yujie, Liu Tianyou, Li Pengyu, Xing Zhichao, Mi Li, He Ting, Wei Tao, Wu Wenshuang
Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China; Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, 610041, China.
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, China; Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Eur J Med Chem. 2025 Jul 5;291:117638. doi: 10.1016/j.ejmech.2025.117638. Epub 2025 Apr 14.
Translation initiation is the first and rate-limiting step in protein synthesis, and its dysregulation is frequently observed in various malignancies. Cap-dependent translation, the predominant form of translation initiation, relies on the coordinated action of eukaryotic translation initiation factors (eIFs), including eIF1, eIF2, eIF4, and others. These factors play critical roles in regulating the efficiency and fidelity of protein synthesis, and their overexpression has been linked to tumor progression, proliferation, and metastasis. Notably, certain eIFs have emerged as potential prognostic markers due to their elevated expression in tumors. Targeting eIFs represents a promising strategy, particularly for cancers characterized by aberrant eIF activity. In this review, we summarize the roles of individual eIFs in cap-dependent translation and discuss their potential as therapeutic targets in cancer treatment. We also highlight recent advances in drug discovery efforts aimed at modulating eIF activity, providing insights into the development of novel anticancer therapies.
翻译起始是蛋白质合成的第一步且是限速步骤,其失调在各种恶性肿瘤中经常可见。帽依赖性翻译是翻译起始的主要形式,它依赖于真核翻译起始因子(eIFs)的协同作用,包括eIF1、eIF2、eIF4等。这些因子在调节蛋白质合成的效率和保真度方面发挥着关键作用,它们的过表达与肿瘤进展、增殖和转移有关。值得注意的是,某些eIFs由于在肿瘤中表达升高而成为潜在的预后标志物。靶向eIFs是一种有前景的策略,特别是对于以eIF活性异常为特征的癌症。在本综述中,我们总结了各个eIFs在帽依赖性翻译中的作用,并讨论它们作为癌症治疗中治疗靶点的潜力。我们还强调了旨在调节eIF活性的药物发现工作的最新进展,为新型抗癌疗法的开发提供见解。