Shibue Tsukasa, Weinberg Robert A
Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, Massachusetts 02142, USA.
Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Nat Rev Clin Oncol. 2017 Oct;14(10):611-629. doi: 10.1038/nrclinonc.2017.44. Epub 2017 Apr 11.
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.
抗癌治疗的成功通常受到耐药性产生的限制。这种获得性耐药部分是由肿瘤内异质性驱动的，即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）概念的提出，假定存在少量具有独特能力播种新肿瘤的CSC亚群，为理解肿瘤内异质性的一个维度提供了框架。这一概念，结合上皮-间质转化（EMT）程序作为CSC表型的关键调节因子的鉴定，为研究肿瘤内异质性的本质和抗癌药物耐药性的可能机制基础提供了机会。事实上，越来越多的证据表明，传统疗法往往无法根除通过激活EMT程序进入CSC状态的癌细胞，从而导致CSC介导的临床复发。在本综述中，我们总结了目前对EMT程序与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。
