Targeting drug-tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells.
Targeting drug-tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells.
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作者：
Song, Xiaohai;Lan, Yang;Zheng, Xiuli;Zhu, Qianyu;Liao, Xuliang;Liu, Kai;Zhang, Weihan;Peng, Qiangbo;Zhu, Yunfeng;Zhao, Linyong;Chen, Xiaolong;Shu, Yang;Yang, Kun;Hu, Jiankun
耐药性仍然是改善接受化疗和靶向治疗的癌症患者预后的最大挑战。大量证据表明，癌细胞亚群可以通过进入没有遗传变异的耐药状态来逃避强烈的选择性药物治疗。这些耐药细胞（DTC）的特点是增殖速度慢和可逆表型。它们存在于肿瘤区域，可能作为耐药表型的储存库。 DTC 的存活受到表观遗传修饰、转录调控、mRNA 翻译重塑、代谢变化、抗凋亡、与肿瘤微环境的相互作用以及信号通路激活的调节。因此，针对 DTC 的调节因子为治疗耐药性肿瘤开辟了一条新途径。在这篇综述中，我们首先概述了 DTC 的共同特征以及 DTC 发展中的调节网络。我们还讨论了针对 DTC 的潜在治疗机会。最后，我们讨论了 DTC 靶向方法克服获得性耐药性的当前挑战和前景。回顾 DTC 研究的最新进展对于发现消除 DTC 的方法至关重要，这可能代表着未来预防耐药性的新治疗策略。耐药细胞（DTC）具有慢周期、干细胞样、EMT样、衰老样和滞育样变化等特征，并且可能是多种耐药突变的储存库。此外，多种调控机制与DT状态的维持相关，如表观基因组、转录和翻译调控；代谢变化；信号通路激活、抗凋亡和肿瘤微环境。
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. Drug‐tolerant cells (DTC) have features including slow‐cycling, stem cell‐like, EMT‐like, senescence‐like and diapause‐like changes, and could be the reservoir of multiple resistant mutations. In addition, multiple regulatory mechanisms are related to the maintenance of the DT state, like epigenomic, transcriptional and translational regulation; metabolic changes; signaling pathway activation, antiapoptosis, and tumor microenvironment.
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影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
64.8
作者：
Boussemart, Lise;Malka-Mahieu, Helene;Vagner, Stephan
通讯作者：
Vagner, Stephan
影响因子：
11.4
作者：
Boila, Liberalis Debraj;Ghosh, Subhadeep;Sengupta, Amitava
通讯作者：
Sengupta, Amitava
影响因子：
14.5
作者：
Alsayed, Reem Khaled M. E.;Sheikhan, Khalid Sultan A. M.;Ahmad, Aamir
通讯作者：
Ahmad, Aamir
影响因子：
6
作者：
BeLow M;Osipo C
通讯作者：
Osipo C