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To wake up cancer stem cells or to let them sleep that is the question

机译:要唤醒癌症干细胞或让它们入睡这就是问题所在

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摘要

Cancer stem cells (CSCs) generate transient‐amplifying cells and thereby contribute to cancer propagation. A fuller understanding of the biological features of CSCs is expected to lead to the development of new anticancer therapies capable of eradicating this life‐threatening disease. Cancer stem cells are known to maintain a non‐proliferative state and to enter the cell cycle only infrequently. Given that conventional anticancer therapies preferentially target dividing cells, CSCs are resistant to such treatments, with those remaining after elimination of bulk cancer cells potentially giving rise to disease relapse and metastasis as they re‐enter the cell cycle after a period of latency. Targeting of the switch between quiescence and proliferation in CSCs is therefore a potential strategy for preventing the reinitiation of malignancy, underscoring the importance of elucidation of the mechanisms by which these cells are maintained in the quiescent state. The fundamental properties of CSCs are thought to be governed cooperatively by internal molecules and cues from the external microenvironment (stem cell niche). Several such intrinsic and extrinsic regulators are responsible for the control of cell cycle progression in CSCs. In this review, we address two opposite approaches to the therapeutic targeting of CSCs – wake‐up and hibernation therapies – that either promote or prevent the entry of CSCs into the cell cycle, respectively, and we discuss the potential advantages and risks of each strategy.
机译:癌症干细胞(CSC)产生瞬时扩增细胞,从而促进癌症的传播。对CSC生物学特性的更全面了解有望导致能够消除这种威胁生命的疾病的新抗癌疗法的发展。已知癌症干细胞会维持非增殖状态,并且很少进入细胞周期。鉴于传统的抗癌疗法优先针对分裂的细胞,因此CSC对这种疗法具有抵抗力,在清除大量癌细胞后残留的CSC可能会在一段时间后重新进入细胞周期,从而导致疾病复发和转移。因此,靶向CSC中的静止和增殖之间的转换是防止恶性肿瘤再次发生的潜在策略,强调阐明将这些细胞维持在静止状态的机制的重要性。 CSC的基本特性被认为由内部分子和来自外部微环境(干细胞小生境)的线索共同控制。几种此类内在和外在调节剂负责控制CSC中的细胞周期进程。在这篇综述中,我们介绍了两种针对CSC的靶向治疗方法-唤醒和冬眠疗法-分别促进或阻止CSC进入细胞周期,并且我们讨论了每种策略的潜在优势和风险。

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