Toxicologic Pathology, Drug Safety Research and Development, Pfizer Inc., Eastern point Road, Groton, CT 06340, USA.
Mutat Res. 2010 Nov 10;693(1-2):3-18. doi: 10.1016/j.mrfmmm.2010.07.008. Epub 2010 Aug 5.
Despite an increased understanding of the molecular pathogenesis of colorectal cancer (CRC) during the past two decades, reliable and robust biomarkers to enable screening, surveillance, and primary prevention of this disease are lacking. CRC diagnosis and therapy remain dependent upon descriptive classification and staging systems, based primarily on morphology and histology. The traditional approach of understanding complex biological systems by studying smaller, discrete units of the whole system has been less fruitful for understanding complex diseases. The implicit assumption of traditional methods, that a single or even only a few factors, play a dominant role in a complex disease might be inadequate when studying multifactorial diseases such as cancer. The burgeoning field of systems biology adopts a holistic approach, wherein the integration of individual parts of the system is sought. The cornerstone of a systems biology approach has been the development of a variety of high-throughput "omics" sciences, including genomics, transcriptomics, proteomics, and metabolomics. This review will focus on the "omics" literature in the field of sporadic human CRC and present examples of how a systems approach has been extremely useful in understanding concepts that would have been difficult to develop using traditional methods.
尽管在过去的二十年中,人们对结直肠癌(CRC)的分子发病机制有了更多的了解,但仍缺乏可靠和稳健的生物标志物来实现对这种疾病的筛查、监测和一级预防。CRC 的诊断和治疗仍然依赖于主要基于形态学和组织学的描述性分类和分期系统。通过研究整个系统中较小的、离散的单元来理解复杂生物系统的传统方法,对于理解复杂疾病的效果较差。传统方法的隐含假设是,在研究癌症等多因素疾病时,单一因素甚至少数因素可能起主导作用,但这可能是不够的。系统生物学领域的蓬勃发展采用了整体方法,其中寻求系统各个部分的整合。系统生物学方法的基石是开发了多种高通量“组学”科学,包括基因组学、转录组学、蛋白质组学和代谢组学。本文将重点介绍散发性人 CRC 领域的“组学”文献,并举例说明系统方法在理解传统方法难以发展的概念方面非常有用。