药物耐药性仍然是为接受化疗和靶向治疗的癌症患者改善预后所面临的最大挑战。逐渐积累的证据表明，肿瘤细胞的一个亚群体能够通过进入一种无需基因变异的耐药状态来逃避强烈的选择性药物治疗。这些耐药性细胞（drug-tolerant cells，DTCs）特征为增殖速度缓慢且可逆转的表型。它们寄居在肿瘤区域，可能作为抗药表型的贮库。DTCs的存活受到表观遗传修饰、转录调节、mRNA翻译重塑、代谢改变、抗凋亡、与肿瘤微环境的相互作用和信号通路的激活等因素的调控。因此，针对DTCs的调控因子为治疗耐药性肿瘤开辟了新途径。在本综述中，我们首先概述了DTCs的共同特征和DTCs发展中的调控网络，接着讨论了针对DTCs的潜在治疗机会。最后，我们探讨了克服获得性耐药性的DTCs靶向方法目前面临的挑战和前景。回顾DTC研究的最新进展对于发现消除DTCs的方法可能在未来预防药物耐药性方面具有重要意义。© 2023 The Authors. MedComm由四川国际医学交流与促进协会（Sichuan International Medical Exchange & Promotion Association，SCIMEA）和John Wiley & Sons Australia, Ltd.发表。

Drug resistance remains the greatest challenge in improving outcomes for cancer patients who receive chemotherapy and targeted therapy. Surmounting evidence suggests that a subpopulation of cancer cells could escape intense selective drug treatment by entering a drug-tolerant state without genetic variations. These drug-tolerant cells (DTCs) are characterized with a slow proliferation rate and a reversible phenotype. They reside in the tumor region and may serve as a reservoir for resistant phenotypes. The survival of DTCs is regulated by epigenetic modifications, transcriptional regulation, mRNA translation remodeling, metabolic changes, antiapoptosis, interactions with the tumor microenvironment, and activation of signaling pathways. Thus, targeting the regulators of DTCs opens a new avenue for the treatment of therapy-resistant tumors. In this review, we first provide an overview of common characteristics of DTCs and the regulating networks in DTCs development. We also discuss the potential therapeutic opportunities to target DTCs. Last, we discuss the current challenges and prospects of the DTC-targeting approach to overcome acquired drug resistance. Reviewing the latest developments in DTC research could be essential in discovering of methods to eliminate DTCs, which may represent a novel therapeutic strategy for preventing drug resistance in the future.© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.