In embryonic development and throughout life, there are some cells can exhibit phenotypic plasticity. Phenotypic plasticity is the ability of cells to differentiate into multiple lineages. In normal development, plasticity is highly regulated whereas cancer cells re-activate this dynamic ability for their own progression. The re-activation of these mechanisms enables cancer cells to acquire a cancer stem cell (CSC) phenotype- a subpopulation of cells with increased ability to survive in a hostile environment and resist therapeutic insults. There are several contributors fuel CSC plasticity in different stages of disease progression such as a complex network of tumour stroma, epidermal microenvironment and different sub-compartments within tumour. These factors play a key role in the transformation of tumour cells from a stable condition to a progressive state. In addition, flexibility in the metabolic state of CSCs helps in disease progression. Moreover, epigenetic changes such as chromatin, DNA methylation could stimulate the phenotypic change of CSCs. Development of resistance to therapy due to highly plastic behaviour of CSCs is a major cause of treatment failure in cancers. However, recent studies explored that plasticity can also expose the weaknesses in CSCs, thereby could be utilized for future therapeutic development. Therefore, in this review, we discuss how cancer cells acquire the plasticity, especially the role of the normal developmental process, tumour microenvironment, and epigenetic changes in the development of plasticity. We further highlight the therapeutic resistance property of CSCs attributed by plasticity. Also, outline some potential therapeutic options against plasticity of CSCs.

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中文翻译：

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癌症干细胞的可塑性：在疾病进展和治疗抗性中的起源和作用。

在胚胎发育和整个生命中，有些细胞可以表现出表型可塑性。表型可塑性是细胞分化成多个谱系的能力。在正常发育中，可塑性受到高度调节，而癌细胞则重新激活这种动态能力以促进自身发展。这些机制的重新激活使癌细胞能够获得癌症干细胞（CSC）表型，这是一种细胞亚群，具有在恶劣环境中生存和抵抗治疗伤害的能力增强。在疾病进展的不同阶段，如肿瘤基质，表皮微环境和肿瘤内不同子室的复杂网络，有多种促成CSC可塑性的因素。这些因素在肿瘤细胞从稳定状态到进展状态的转化中起关键作用。此外，CSCs代谢状态的灵活性有助于疾病进展。此外，表观遗传变化，例如染色质，DNA甲基化可以刺激CSCs的表型变化。由于CSC的高度可塑性行为而引起的对治疗的抵抗力的发展是癌症治疗失败的主要原因。但是，最近的研究探索了可塑性也可以暴露CSC的弱点，从而可以用于未来的治疗开发。因此，在这篇综述中，我们讨论了癌细胞如何获得可塑性，特别是正常发育过程，肿瘤微环境以及可塑性发展中表观遗传学变化的作用。我们进一步强调可塑性归因于CSCs的治疗耐药性。此外，概述一些潜在的针对CSC可塑性的治疗选择。

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