文章：

表型可塑性是黑色素瘤进展和治疗抵抗的推动者

Phenotype plasticity as enabler of melanoma progression and therapy resistance

原文发布日期：2019-06-17

DOI: 10.1038/s41568-019-0154-4

类型: Review Article

开放获取: 否

英文摘要：

Malignant melanoma is notorious for its inter- and intratumour heterogeneity, based on transcriptionally distinct melanoma cell phenotypes. It is thought that these distinct phenotypes are plastic in nature and that their transcriptional reprogramming enables heterogeneous tumours both to undergo different stages of melanoma progression and to adjust to drug exposure during treatment. Recent advances in genomic technologies and the rapidly expanding availability of large gene expression datasets have allowed for a refined definition of the gene signatures that characterize these phenotypes and have revealed that phenotype plasticity plays a major role in the resistance to both targeted therapy and immunotherapy. In this Review we discuss the definition of melanoma phenotypes through particular transcriptional states and reveal the prognostic relevance of the related gene expression signatures. We review how the establishment of phenotypes is controlled and which roles phenotype plasticity plays in melanoma development and therapy. Because phenotype plasticity in melanoma bears a great resemblance to epithelial–mesenchymal transition, the lessons learned from melanoma will also benefit our understanding of other cancer types.

摘要翻译： 

恶性黑色素瘤以其基于转录水平不同的黑色素瘤细胞表型而具有的肿瘤间和肿瘤内异质性著称。这些不同的表型本质上是可塑的，它们的转录重编程使得异质性肿瘤既能够经历黑色素瘤进展的不同阶段，也能够适应治疗期间的药物暴露。基因组技术的最新进展以及大型基因表达数据集的迅速扩展，使得对这些表型特征基因标记的定义更加精确，并揭示了表型可塑性在靶向治疗和免疫治疗耐药性中起主要作用。在本篇综述中，我们通过特定的转录状态讨论黑色素瘤表型的定义，并揭示相关基因表达特征的预后意义。我们回顾了表型的建立是如何被控制的，以及表型可塑性在黑色素瘤的发展和治疗中扮演了哪些角色。由于黑色素瘤中的表型可塑性与上皮-间质转化非常相似，从黑色素瘤中获得的经验也将有助于我们对其他癌症类型的理解。

原文链接：

Phenotype plasticity as enabler of melanoma progression and therapy resistance