Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Department of Medical Biophysics, University Health Network, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology University Health Network, Toronto, Ontario, Canada.
J Thorac Oncol. 2021 Nov;16(11):1798-1809. doi: 10.1016/j.jtho.2021.07.017. Epub 2021 Aug 3.
A minor population of cancer cells may evade cell death from chemotherapy and targeted therapy by entering a reversible slow proliferation state known as the drug tolerant persister (DTP) state. This DTP state can allow cancer cells to survive drug therapy long enough for additional mechanisms of acquired drug resistance to develop. Thus, cancer persistence is a major obstacle to curing cancers, where insight into the biology of DTP cells and therapeutic strategies targeting this mechanism can have considerable clinical implications. There is emerging evidence that DTP cells adapt to new environments through epigenomic modification, transcriptomic regulation, flexible energy metabolism, and interactions with the tumor microenvironment. Herein, we review and discuss the various proposed mechanisms of cancer persister cells and the molecular features underlying the DTP state, with insights into the potential therapeutic strategies to conquer DTP cells and prevent cancer recurrence or therapeutic failures.
一小部分癌细胞可能通过进入一种可逆的缓慢增殖状态，即所谓的药物耐受持久状态（DTP），从而逃避化疗和靶向治疗引起的细胞死亡。这种 DTP 状态可以使癌细胞在药物治疗中存活足够长的时间，从而使获得性耐药机制得以发展。因此，癌症的持续存在是治愈癌症的主要障碍，深入了解 DTP 细胞的生物学特性以及针对这种机制的治疗策略具有重要的临床意义。有新的证据表明，DTP 细胞通过表观基因组修饰、转录组调节、灵活的能量代谢以及与肿瘤微环境的相互作用来适应新的环境。在此，我们综述并讨论了各种关于癌症持久细胞的形成机制和 DTP 状态的分子特征，并深入探讨了克服 DTP 细胞和预防癌症复发或治疗失败的潜在治疗策略。
