Cabanos Heidie Frisco, Hata Aaron N
Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Cancers (Basel). 2021 May 28;13(11):2666. doi: 10.3390/cancers13112666.
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.
耐药性可能是改善接受靶向治疗的癌症患者治疗效果方面最大的挑战。越来越清楚的是，“持久性细胞”是在癌症群体中发现的一类耐药细胞亚群，在耐药性的发展中起关键作用。持久性细胞能够在治疗下维持活力，但通常增殖缓慢或处于休眠状态。这些细胞没有典型的耐药驱动改变，并且它们的部分耐药表型是短暂的，在去除药物后是可逆的。在临床上，持久性细胞状态最接近微小残留病，如果治疗中断或因持续治疗出现获得性耐药，就可能发生复发。因此，消除持久性细胞对于改善癌症患者的治疗效果至关重要。以肺癌靶向治疗作为主要范例，本综述将概述耐药持久性细胞的特征、与耐药性相关的机制以及针对肿瘤中这一持久性细胞群体的潜在治疗机会。
