Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.
Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.
Adv Cancer Res. 2019;141:43-84. doi: 10.1016/bs.acr.2018.12.002. Epub 2019 Jan 16.
Dormancy occurs when cells remain viable but stop proliferating. When most of a cancer population undergoes this phenomenon, the result is called tumor dormancy, and when a single cancer cell undergoes this process, it is termed quiescence. Cancer stem cells (CSCs) share several overlapping characteristics and signaling pathways with dormant cancer cells, including therapy resistance, and an ability to metastasize and evade the immune system. Cancer cells can be broadly grouped into dormancy-competent CSCs (DCCs), cancer-repopulating cells (CRCs), dormancy-incompetent CSCs and disseminated tumor cells (DTCs). The settings in which cancer cells exploit the dormancy phase to survive and adapt are: (i) primary cancer dormancy; (ii) metastatic dormancy; (iii) therapy-induced dormancy; and (iv) immunologic dormancy. Dormancy, therapy resistance and plasticity of CSCs are fundamentally interconnected processes mediated through mechanisms involving reversible genetic alterations. Niches including metastatic, bone marrow, and perivascular are known to harbor dormant cancer cells. Mechanisms of dormancy induction are complex and multi-factorial and can involve angiogenic switching, addictive oncogene inhibition, immunoediting, anoikis, therapy, autophagy, senescence, epigenetic, and biophysical regulation. Therapy can have opposing effects on cancer cells with respect to dormancy; some therapies can induce dormancy, while others can reactivate dormant cells. There is a lack of consensus relative to the value of therapy-induced dormancy, i.e., some researchers view dormancy induction as a beneficial strategy as it can lead to metastasis inhibition, while others argue that reactivating dormant cancer cells and then eliminating them through therapy are a better approach. More focused investigations of intrinsic cell kinetics and environmental dynamics that promote and maintain cancer cells in a dormant state, and the long-term consequences of dormancy are critical for improving current therapeutic treatment outcomes.
休眠是指细胞仍然存活但停止增殖的状态。当大部分癌细胞发生这种现象时，结果称为肿瘤休眠；而当单个癌细胞发生这种过程时，则称为静止。癌症干细胞（CSC）与休眠癌细胞具有几个重叠的特征和信号通路，包括治疗耐药性以及转移和逃避免疫系统的能力。癌细胞可以广泛分为休眠能力的 CSC（DCC）、癌症再增殖细胞（CRC）、休眠能力不足的 CSC 和播散性肿瘤细胞（DTC）。癌细胞利用休眠期生存和适应的环境包括：（i）原发性癌症休眠；（ii）转移性休眠；（iii）治疗诱导的休眠；和（iv）免疫休眠。CSC 的休眠、治疗耐药性和可塑性是通过涉及可逆遗传改变的机制相互关联的基本过程。已知转移性、骨髓和血管周围等部位存在休眠癌细胞。休眠诱导的机制复杂且多因素，可能涉及血管生成转换、成瘾性致癌基因抑制、免疫编辑、失巢凋亡、治疗、自噬、衰老、表观遗传和生物物理调节。治疗对癌细胞的休眠状态可能具有相反的影响；一些治疗可以诱导休眠，而另一些则可以重新激活休眠细胞。关于治疗诱导休眠的价值存在缺乏共识，即一些研究人员认为休眠诱导是一种有益的策略，因为它可以抑制转移，而另一些人则认为重新激活休眠癌细胞并通过治疗消除它们是一种更好的方法。更集中地研究促进和维持癌细胞处于休眠状态的内在细胞动力学和环境动态，以及休眠的长期后果，对于改善当前的治疗治疗效果至关重要。
