Buikhuisen Joyce Y, Torang Arezo, Medema Jan Paul
Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Oncode Institute, Amsterdam, The Netherlands.
Oncogenesis. 2020 Jul 9;9(7):66. doi: 10.1038/s41389-020-00250-6.
Colon cancer inter-tumour heterogeneity is installed on multiple levels, ranging from (epi)genetic driver events to signalling pathway rewiring reflected by differential gene expression patterns. Although the existence of heterogeneity in colon cancer has been recognised for a longer period of time, it is sparingly incorporated as a determining factor in current clinical practice. Here we describe how unsupervised gene expression-based classification efforts, amongst which the consensus molecular subtypes (CMS), can stratify patients in biological subgroups associated with distinct disease outcome and responses to therapy. We will discuss what is needed to extend these subtyping efforts to the clinic and we will argue that preclinical models recapitulate CMS subtypes and can be of vital use to increase our understanding of treatment response and resistance and to discover novel targets for therapy.
结肠癌肿瘤间的异质性在多个层面上存在，从（表观）遗传驱动事件到由差异基因表达模式反映的信号通路重塑。尽管结肠癌异质性的存在已被认识较长时间，但在当前临床实践中，它很少被作为一个决定性因素纳入考虑。在此，我们描述了基于无监督基因表达的分类方法，其中包括共识分子亚型（CMS），如何将患者分层为与不同疾病结局和治疗反应相关的生物学亚组。我们将讨论将这些亚型分类方法扩展到临床需要哪些条件，并且我们认为临床前模型能够重现CMS亚型，对于增进我们对治疗反应和耐药性的理解以及发现新的治疗靶点至关重要。
