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利用翻译机制治疗癌症:翻译因子作为有前途的靶点。

Exploiting Translation Machinery for Cancer Therapy: Translation Factors as Promising Targets.

机构信息

Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

出版信息

Int J Mol Sci. 2024 Oct 9;25(19):10835. doi: 10.3390/ijms251910835.

Abstract

Eukaryotic protein translation has slowly gained the scientific community's attention for its advanced and powerful therapeutic potential. However, recent technical developments in studying ribosomes and global translation have revolutionized our understanding of this complex multistep process. These developments have improved and deepened the current knowledge of mRNA translation, sparking excitement and new possibilities in this field. Translation factors are crucial for maintaining protein synthesis homeostasis. Since actively proliferating cancer cells depend on protein synthesis, dysregulated protein translation is central to tumorigenesis. Translation factors and their abnormal expressions directly affect multiple oncogenes and tumor suppressors. Recently, small molecules have been used to target translation factors, resulting in translation inhibition in a gene-specific manner, opening the door for developing translation inhibitors that can lead to novel chemotherapeutic drugs for treating multiple cancer types caused by dysregulated translation machinery. This review comprehensively summarizes the involvement of translation factors in tumor progression and oncogenesis. Also, it sheds light on the evolution of translation factors as novel drug targets for developing future therapeutic drugs for treating cancer.

摘要

真核生物蛋白翻译因其先进而强大的治疗潜力,逐渐引起科学界的关注。然而,近年来核糖体和全球翻译的技术发展彻底改变了我们对这一复杂多步骤过程的理解。这些发展提高并深化了我们对 mRNA 翻译的现有认识,为该领域带来了新的活力和可能性。翻译因子对于维持蛋白质合成的动态平衡至关重要。由于活跃增殖的癌细胞依赖于蛋白质合成,因此失调的蛋白质翻译是肿瘤发生的核心。翻译因子及其异常表达直接影响多种癌基因和肿瘤抑制基因。最近,小分子已被用于靶向翻译因子,以基因特异性方式抑制翻译,为开发翻译抑制剂开辟了道路,这些抑制剂可用于治疗多种由翻译机制失调引起的癌症类型。本综述全面总结了翻译因子在肿瘤进展和致癌中的作用。此外,它还揭示了翻译因子作为新型药物靶点的进化,为开发治疗癌症的未来治疗药物提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4324/11477148/b5c093cccdc8/ijms-25-10835-g001.jpg

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