Werner Henrica M J, Mills Gordon B, Ram Prahlad T
Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, P. O. Box 7800, 5053 Bergen, Norway.
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1484, Houston, TX 77030, USA.
Nat Rev Clin Oncol. 2014 Mar;11(3):167-76. doi: 10.1038/nrclinonc.2014.6. Epub 2014 Feb 4.
Traditionally, scientific research has focused on studying individual events, such as single mutations, gene function, or the effect that mutating one protein has on a biological phenotype. A range of technologies is beginning to provide information that will enable a holistic view of how genomic and epigenetic aberrations in cancer cells can alter the homeostasis of signalling networks within these cells, between cancer cells and the local microenvironment, and at the organ and organism level. This process, termed Systems Biology, needs to be integrated with an iterative approach wherein hypotheses and predictions that arise from modelling are refined and constrained by experimental evaluation. Systems biology approaches will be vital for developing and implementing effective strategies to deliver personalized cancer therapy. Specifically, these approaches will be important to select those patients who are most likely to benefit from targeted therapies and for the development and implementation of rational combinatorial therapies. Systems biology can help to increase therapy efficacy or bypass the emergence of resistance, thus converting the current-often short term-effects of targeted therapies into durable responses, ultimately to improve patient quality of life and provide a cure.
传统上,科学研究专注于单个事件的研究,比如单个突变、基因功能,或者某一蛋白质突变对生物表型的影响。一系列技术开始提供相关信息,使人们能够全面了解癌细胞中的基因组和表观遗传畸变如何改变这些细胞内、癌细胞与局部微环境之间以及器官和生物体水平上信号网络的稳态。这个过程被称为系统生物学,需要与一种迭代方法相结合,在这种方法中,由建模产生的假设和预测通过实验评估得到完善和约束。系统生物学方法对于开发和实施有效的个性化癌症治疗策略至关重要。具体而言,这些方法对于选择那些最有可能从靶向治疗中获益的患者以及开发和实施合理的联合治疗非常重要。系统生物学有助于提高治疗效果或避免耐药性的出现,从而将目前靶向治疗通常的短期效果转化为持久反应,最终改善患者生活质量并实现治愈。