Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.
Research Center for Translational Medicine, Cancer Stem Cell Institute, East Hospital, Tongji University School of Medicine, Shanghai, China.
Semin Cancer Biol. 2022 Jan;78:90-103. doi: 10.1016/j.semcancer.2021.04.021. Epub 2021 May 9.
It is increasingly appreciated that cancer cell heterogeneity and plasticity constitute major barriers to effective clinical treatments and long-term therapeutic efficacy. Research in the past two decades suggest that virtually all treatment-naive human cancers harbor subsets of cancer cells that possess many of the cardinal features of normal stem cells. Such stem-like cancer cells, operationally defined as cancer stem cells (CSCs), are frequently quiescent and dynamically change and evolve during tumor progression and therapeutic interventions. Intrinsic tumor cell heterogeneity is reflected in a different aspect in that tumors also harbor a population of slow-cycling cells (SCCs) that are not in the proliferative cell cycle and thus are intrinsically refractory to anti-mitotic drugs. In this Perspective, we focus our discussions on SCCs in cancer and on various methodologies that can be employed to enrich and purify SCCs, compare the similarities and differences between SCCs, CSCs and cancer cells undergoing EMT, and present evidence for the involvement of SCCs in surviving anti-neoplastic treatments, mediating tumor relapse, maintaining tumor dormancy and mediating metastatic dissemination. Our discussions make it clear that an in-depth understanding of the biological properties of SCCs in cancer will be instrumental to developing new therapeutic strategies to prevent tumor relapse and distant metastasis.
越来越多的人认识到，癌细胞异质性和可塑性是有效临床治疗和长期治疗效果的主要障碍。过去二十年的研究表明，几乎所有未经治疗的人类癌症都存在具有正常干细胞许多主要特征的癌细胞亚群。这种具有干细胞样特征的癌细胞，通常被定义为癌症干细胞（CSC），通常处于静止状态，并在肿瘤进展和治疗干预过程中动态变化和演变。内在的肿瘤细胞异质性在不同方面反映出来，即肿瘤还存在一群缓慢循环的细胞（SCC），它们不在增殖细胞周期中，因此本质上对抗有丝分裂药物具有抗性。在本观点中，我们重点讨论了癌症中的 SCC 以及可用于富集和纯化 SCC 的各种方法，比较了 SCC、CSC 和发生 EMT 的癌细胞之间的相似性和差异，并提供了 SCC 参与抗瘤治疗、介导肿瘤复发、维持肿瘤休眠和介导转移扩散的证据。我们的讨论清楚地表明，深入了解癌症中 SCC 的生物学特性对于开发新的治疗策略以预防肿瘤复发和远处转移将是至关重要的。
