McIntyre Rebecca E, Buczacki Simon J A, Arends Mark J, Adams David J
Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Cambridge, UK.
Bioessays. 2015 Aug;37(8):909-20. doi: 10.1002/bies.201500032. Epub 2015 Jun 26.
In this review, we discuss the application of mouse models to the identification and pre-clinical validation of novel therapeutic targets in colorectal cancer, and to the search for early disease biomarkers. Large-scale genomic, transcriptomic and epigenomic profiling of colorectal carcinomas has led to the identification of many candidate genes whose direct contribution to tumourigenesis is yet to be defined; we discuss the utility of cross-species comparative 'omics-based approaches to this problem. We highlight recent progress in modelling late-stage disease using mice, and discuss ways in which mouse models could better recapitulate the complexity of human cancers to tackle the problem of therapeutic resistance and recurrence after surgical resection.
在本综述中,我们讨论了小鼠模型在结直肠癌新治疗靶点的鉴定和临床前验证以及早期疾病生物标志物寻找方面的应用。对结直肠癌进行大规模的基因组、转录组和表观基因组分析已鉴定出许多候选基因,但其对肿瘤发生的直接作用尚待确定;我们讨论了基于跨物种比较“组学”方法解决这一问题的效用。我们强调了利用小鼠对晚期疾病建模的最新进展,并讨论了小鼠模型如何能更好地重现人类癌症的复杂性,以解决手术切除后治疗耐药性和复发的问题。