Stem Cell Biology Laboratory, Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University, Lakeside Campus, Subang Jaya, Selangor, Malaysia.
Stem Cell Rev Rep. 2020 Dec;16(6):1185-1207. doi: 10.1007/s12015-020-10031-8.
Quiescence in cancer cells is considered a therapeutic challenge as it confers dormancy in tumour, hence circumventing inherent anti-neoplastic surveillance system and standard-of-care cancer therapeutics including chemotherapy and radiotherapy. Since majority of the therapeutics target actively proliferating cancer cells, cancer cells eventually develop quiescent nature as mechanism of survival and cancer progression under both niche and therapeutic pressures. Quiescence state in cancer cells, eventually, confers resistant and aggressive nature to conventional cancer therapies, resulting in disease progression and relapse. Therefore, targeting quiescent cancer cells or cancer stem cells is a promising therapeutic approach, however an extensive review of the relevant information is needed in order to device an effective therapy. While the evidence of quiescence regulation in CSCs is rather a complex molecular and cellular network, herein, we aim to provide a comprehensive understanding of both intrinsic and extrinsic regulation in association with the function of CSCs. Findings on induction of quiescent state in CSCs population, its regulation at both cellular and molecular level, key molecular regulators, cellular events and processes including potential targets to develop therapeutics are extensively reviewed. This review also highlights the impact of CSC plasticity on quiescence which capturing the key challenge of targeting the cells in this state. Beyond understanding the mechanisms underlying quiescence nature of cancer cells, this review provides insightful perspective and future direction on insight in targeting these populations, hence collapse the tumour dormancy programme in order to eradicate tumour mass as a whole. Capability of CSCs to establish quiescent state as a mechanism of survival during unfavorable conditions, as well as its impact in cancer progression and subsequent relapse, including the potential therapeutic strategy to eradicate this CSCs sub-population in the tumor mass as an effective cancer therapy.
癌细胞的静止状态被认为是一个治疗挑战，因为它使肿瘤处于休眠状态，从而规避了肿瘤固有的抗肿瘤监测系统和标准的癌症治疗方法，包括化疗和放疗。由于大多数治疗方法针对的是活跃增殖的癌细胞，因此，在微环境和治疗压力下，癌细胞最终会发展出静止状态，作为其生存和癌症进展的机制。癌细胞的静止状态最终会使传统癌症治疗方法产生耐药性和侵袭性，导致疾病进展和复发。因此，靶向静止期的癌细胞或癌症干细胞是一种很有前途的治疗方法，但需要对相关信息进行广泛的综述，才能制定出有效的治疗方法。虽然 CSCs 中静止状态的调节证据相当复杂，涉及分子和细胞网络，但在此，我们旨在提供对 CSCs 中内在和外在调节与功能相关的全面理解。本文广泛综述了诱导 CSCs 群体进入静止状态、其在细胞和分子水平上的调节、关键分子调节剂、细胞事件和过程（包括开发治疗方法的潜在靶点）的研究发现。这篇综述还强调了 CSC 可塑性对静止状态的影响，这是捕捉靶向这些细胞状态的关键挑战。除了了解癌细胞静止状态的机制外，本文还为靶向这些细胞群体提供了有见地的观点和未来方向，从而瓦解肿瘤休眠程序，以整体消除肿瘤。CSC 建立静止状态作为在不利条件下生存的机制的能力，以及其在癌症进展和随后复发中的影响，包括消除肿瘤内这种 CSCs 亚群的潜在治疗策略作为一种有效的癌症治疗方法。
