Andres Sarah F, Williams Kathy N, Rustgi Anil K
Division of Gastroenterology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Curr Colorectal Cancer Rep. 2018 Apr;14(2):69-79. doi: 10.1007/s11888-018-0403-z. Epub 2018 Mar 1.
Metastatic colorectal cancer (CRC) is a vexing clinical problem. In contrast to early stage disease, once CRC metastasizes to other organs, long-term survival is compromised. We seek to review the molecular pathogenesis, animal models, and functional genomics for an enhanced understanding of how CRC metastasizes and how this can be exploited therapeutically.
Mouse models may recapitulate certain aspects of metastatic human CRC and allow for studies to identify regulators of metastasis. Modulation of transcription factors, onco-proteins, or tumor suppressors have been identified to activate known metastatic pathways. CD44 variants, microRNAs and RNA binding proteins are emerging as metastatic modulators.
CRC metastasis is a multi-faceted and heterogeneous disease. Despite common pathways contributing to metastatic development, there are numerous variables that modulate metastatic signals in subsets of patients. It is paramount that studies continue to investigate metastatic drivers, enhancers and inhibitors in CRC to develop therapeutic targets and improve disease outcomes.
转移性结直肠癌(CRC)是一个棘手的临床问题。与早期疾病不同,一旦CRC转移至其他器官,长期生存就会受到影响。我们旨在综述分子发病机制、动物模型和功能基因组学,以加深对CRC转移方式以及如何通过治疗手段加以利用的理解。
小鼠模型可能会概括转移性人类CRC的某些方面,并有助于开展研究以确定转移调节因子。已确定转录因子、癌蛋白或肿瘤抑制因子的调节作用可激活已知的转移途径。CD44变体、微小RNA和RNA结合蛋白正成为转移调节因子。
CRC转移是一种多方面且异质性的疾病。尽管存在促成转移发展的共同途径,但仍有众多变量调节部分患者亚群中的转移信号。继续开展研究以探究CRC中的转移驱动因素、增强因素和抑制因素,从而开发治疗靶点并改善疾病转归至关重要。