Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy. This comprehensive review examines the complex relationship between USPs and drug resistance mechanisms, focusing on specific treatment strategies and highlighting the influence of USPs on DNA damage repair, apoptosis, characteristics of cancer stem cells, immune evasion, and other crucial biological functions. Additionally, the review highlights the potential clinical significance of USP inhibitors as a means to counter drug resistance in cancer treatment. By inhibiting particular USP, cancer cells can become more susceptible to a variety of anti-cancer drugs. The integration of USP inhibitors with current anti-cancer therapies offers a promising strategy to circumvent drug resistance. Therefore, this review emphasizes the importance of USPs as viable therapeutic targets and offers insight into fruitful directions for future research and drug development. Targeting USPs presents an effective method to combat drug resistance across various cancer types, leading to enhanced treatment strategies and better patient outcomes.

中文翻译：

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癌症中泛素特异性蛋白酶（USP）介导的耐药机制和治疗策略：新方向和治疗选择

耐药性是癌症治疗的一个重大障碍，强调了发现新治疗靶点的必要性。泛素特异性蛋白酶 (USP) 是去泛素化酶的一个亚类，在蛋白质去泛素化中发挥着关键作用。随着科学研究的进步，USP 已被认为是化疗、靶向治疗、免疫治疗和放疗等一系列治疗方式耐药性的关键调节剂。这篇全面的综述探讨了 USP 与耐药机制之间的复杂关系，重点关注具体的治疗策略，并强调 USP 对 DNA 损伤修复、细胞凋亡、癌症干细胞特征、免疫逃避和其他重要生物学功能的影响。此外，该综述强调了 USP 抑制剂作为对抗癌症治疗中耐药性的一种手段的潜在临床意义。通过抑制特定的 USP，癌细胞可以变得对多种抗癌药物更敏感。 USP 抑制剂与当前抗癌疗法的整合为规避耐药性提供了一种有前景的策略。因此，本综述强调了 USP 作为可行治疗靶点的重要性，并为未来研究和药物开发提供了富有成效的方向。针对 USP 提供了一种对抗各种癌症类型耐药性的有效方法，从而增强治疗策略并改善患者预后。