Ras proteins are pivotal in the regulation of cell proliferation signals, and their dysregulation is intricately linked to the pathogenesis of various malignancies. Peptide inhibitors hold distinct advantages in targeting Ras proteins, attributable to their extensive binding domains, which result from the smooth surfaces of the proteins. The array of specific strategies includes the employment of full hydrocarbon chains, cyclic peptides, linear peptides, and N-terminal nucleation polypeptides. These methods effectively suppress the Ras signaling pathway through distinct mechanisms, highlighting their potential as anti-neoplastic agents. Moreover, cutting-edge methodologies, including the N-terminal aspartate nucleation strategy and the utilization of hydrocarbon-stapled peptides, are transforming the landscape of therapeutics aimed at Ras proteins. These innovations highlight the promise of peptide libraries and combinatorial chemistry in augmenting binding affinity, specificity, and cellular permeability, which are pivotal for the development of potent anti-cancer agents. The incorporation of dual therapeutic strategies, such as the synergy between peptide inhibitors and conventional chemotherapy or the use of radiotherapy enhancers, emerges as a compelling strategy to bolster the efficacy of cancer treatments targeting the Ras-MAPK pathway. Furthermore, recent studies have demonstrated that Ras-targeting stabilized peptides can amplify the radio-sensitivity of cancer cells, offering an innovative approach to enhance the efficacy of radiation therapy within cancer management.

中文翻译：

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癌症治疗中靶向野生型 Ras 蛋白相互作用的肽抑制剂的最新进展。


Ras 蛋白在细胞增殖信号的调节中起着关键作用，其失调与各种恶性肿瘤的发病机制有着错综复杂的联系。肽抑制剂在靶向 Ras 蛋白方面具有明显的优势，这归因于其广泛的结合结构域，这些结合结构域是由蛋白质的光滑表面产生的。一系列具体策略包括使用全烃链、环肽、线性肽和 N 末端成核多肽。这些方法通过不同的机制有效抑制 Ras 信号通路，突出了它们作为抗肿瘤药物的潜力。此外，包括 N 末端天冬氨酸成核策略和碳氢化合物吻合肽利用在内的尖端方法正在改变针对 Ras 蛋白的治疗格局。这些创新突出了肽库和组合化学在增强结合亲和力、特异性和细胞通透性方面的前景，这对于开发有效的抗癌药物至关重要。双重治疗策略的结合，例如肽抑制剂和常规化疗之间的协同作用或使用放疗增强剂，成为增强针对 Ras-MAPK 通路的癌症治疗疗效的令人信服的策略。此外，最近的研究表明，靶向 Ras 的稳定肽可以放大癌细胞的放射敏感性，提供了一种创新方法来提高癌症管理中放射治疗的疗效。