The success of anticancer therapy is usually limited by the development of drug resistance. Such acquired resistance is driven, in part, by intratumoural heterogeneity — that is, the phenotypic diversity of cancer cells co-inhabiting a single tumour mass. The introduction of the cancer stem cell (CSC) concept, which posits the presence of minor subpopulations of CSCs that are uniquely capable of seeding new tumours, has provided a framework for understanding one dimension of intratumoural heterogeneity. This concept, taken together with the identification of the epithelial-to-mesenchymal transition (EMT) programme as a critical regulator of the CSC phenotype, offers an opportunity to investigate the nature of intratumoural heterogeneity and a possible mechanistic basis for anticancer drug resistance. In fact, accumulating evidence indicates that conventional therapies often fail to eradicate carcinoma cells that have entered the CSC state via activation of the EMT programme, thereby permitting CSC-mediated clinical relapse. In this Review, we summarize our current understanding of the link between the EMT programme and the CSC state, and also discuss how this knowledge can contribute to improvements in clinical practice.

中文翻译：

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EMT，CSC和耐药性：机理联系和临床意义

抗癌治疗的成功通常受到耐药性发展的限制。这种获得性抗药性部分是由肿瘤内异质性驱动的，即异质性共同存在于单个肿瘤块中的癌细胞的表型多样性。癌症干细胞（CSC）概念的引入（它假设存在独特地能够播种新肿瘤的CSC的次要亚群），为理解肿瘤内异质性的一个维度提供了框架。该概念与上皮到间充质转变（EMT）程序的确定一起作为CSC表型的关键调节剂，为研究肿瘤内异质性的性质以及抗癌药物耐药性的可能机制奠定了基础。实际上，越来越多的证据表明，传统疗法通常无法通过激活EMT程序根除已经进入CSC状态的癌细胞，从而允许CSC介导的临床复发。在这篇综述中，我们总结了我们目前对EMT计划与CSC状态之间联系的理解，并讨论了这些知识如何有助于改善临床实践。