Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer.
Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer.
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DOI：
10.3390/cancers13112666
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发表时间：
2021-05-28
期刊：
影响因子：
5.2
通讯作者：
Hata AN
中科院分区：
文献类型：
--
作者：
Cabanos HF;Hata AN
对分子靶向治疗的获得性耐药性仍然是癌症治疗中的主要挑战。已经假设，没有真正的耐药机制的耐药（或"持久"）细胞可以在初始药物治疗中存活，并随着时间的推移经历进一步的进化以获得导致癌症复发的耐药机制。在这篇综述中，我们将讨论最近在体外，体内和临床研究揭示这些细胞的机制和脆弱性的见解。耐药性可能是改善接受靶向治疗的癌症患者预后的最大挑战。越来越清楚的是，“坚持者”，一种在癌症人群中发现的耐药细胞亚群，在耐药性的发展中起着关键作用。在治疗下，持续性能够保持活力，但通常是缓慢循环或休眠。这些细胞不具有经典的耐药驱动改变，并且它们的部分耐药表型在去除药物后是暂时的和可逆的。在临床中，持续状态最接近于微小残留病，如果治疗中断或如果持续治疗产生获得性耐药性，则可能发生复发。因此，消除持续存在的细胞对于改善癌症患者的预后至关重要。以肺癌靶向治疗为主要范例，本文将概述耐药持续细胞的特征、与耐药相关的机制以及靶向肿瘤持续细胞群体的潜在治疗机会。
Acquired resistance to molecularly targeted therapies remains a major challenge in the treatment of cancer. It has been hypothesized that drug-tolerant (or “persister”) cells without bona fide resistance mechanisms may survive initial drug treatment and undergo further evolution over time to acquire resistance mechanisms leading to cancer relapse. In this review, we will discuss insights into mechanisms and vulnerabilities of these cells revealed by recent in vitro, in vivo, and clinical studies. Drug resistance is perhaps the greatest challenge in improving outcomes for cancer patients undergoing treatment with targeted therapies. It is becoming clear that “persisters,” a subpopulation of drug-tolerant cells found in cancer populations, play a critical role in the development of drug resistance. Persisters are able to maintain viability under therapy but are typically slow cycling or dormant. These cells do not harbor classic drug resistance driver alterations, and their partial resistance phenotype is transient and reversible upon removal of the drug. In the clinic, the persister state most closely corresponds to minimal residual disease from which relapse can occur if treatment is discontinued or if acquired drug resistance develops in response to continuous therapy. Thus, eliminating persister cells will be crucial to improve outcomes for cancer patients. Using lung cancer targeted therapies as a primary paradigm, this review will give an overview of the characteristics of drug-tolerant persister cells, mechanisms associated with drug tolerance, and potential therapeutic opportunities to target this persister cell population in tumors.
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影响因子：
50.3
作者：
Dravis C;Chung CY;Lytle NK;Herrera-Valdez J;Luna G;Trejo CL;Reya T;Wahl GM
通讯作者：
Wahl GM
影响因子：
82.9
作者：
Bivona TG;Doebele RC
通讯作者：
Doebele RC
影响因子：
8.8
作者：
通讯作者：
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影响因子：
8
作者：
Endo, H.;Okami, J.;Inoue, M.
通讯作者：
Inoue, M.
影响因子：
50.3
作者：
Eberl, Markus;Mangelberger, Doris;Wong, Sunny Y.
通讯作者：
Wong, Sunny Y.