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系统生物学能否推动临床精准肿瘤学的发展？

Can Systems Biology Advance Clinical Precision Oncology?

作者信息

Rocca Andrea, Kholodenko Boris N

机构信息

Hygiene and Public Health, Local Health Unit of Romagna, 47121 Forlì, Italy.

Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.

出版信息

Cancers (Basel). 2021 Dec 16;13(24):6312. doi: 10.3390/cancers13246312.

DOI:10.3390/cancers13246312
PMID:34944932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8699328/
Abstract

Precision oncology is perceived as a way forward to treat individual cancer patients. However, knowing particular cancer mutations is not enough for optimal therapeutic treatment, because cancer genotype-phenotype relationships are nonlinear and dynamic. Systems biology studies the biological processes at the systems' level, using an array of techniques, ranging from statistical methods to network reconstruction and analysis, to mathematical modeling. Its goal is to reconstruct the complex and often counterintuitive dynamic behavior of biological systems and quantitatively predict their responses to environmental perturbations. In this paper, we review the impact of systems biology on precision oncology. We show examples of how the analysis of signal transduction networks allows to dissect resistance to targeted therapies and inform the choice of combinations of targeted drugs based on tumor molecular alterations. Patient-specific biomarkers based on dynamical models of signaling networks can have a greater prognostic value than conventional biomarkers. These examples support systems biology models as valuable tools to advance clinical and translational oncological research.

摘要

精准肿瘤学被视为治疗个体癌症患者的一条前进道路。然而，仅仅了解特定的癌症突变对于实现最佳治疗是不够的，因为癌症基因型与表型的关系是非线性且动态的。系统生物学在系统层面研究生物过程，运用一系列技术，从统计方法到网络重建与分析，再到数学建模。其目标是重建生物系统复杂且往往违反直觉的动态行为，并定量预测它们对环境扰动的反应。在本文中，我们综述了系统生物学对精准肿瘤学的影响。我们展示了信号转导网络分析如何能够剖析对靶向治疗的耐药性，并根据肿瘤分子改变为靶向药物组合的选择提供依据。基于信号网络动态模型的患者特异性生物标志物可能比传统生物标志物具有更大的预后价值。这些例子支持系统生物学模型作为推进临床和转化肿瘤学研究的有价值工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f06/8699328/cccb65af7c8d/cancers-13-06312-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f06/8699328/cd0910615012/cancers-13-06312-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f06/8699328/21f9b09e0b27/cancers-13-06312-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f06/8699328/cd615405d7f2/cancers-13-06312-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f06/8699328/cccb65af7c8d/cancers-13-06312-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f06/8699328/cd0910615012/cancers-13-06312-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f06/8699328/21f9b09e0b27/cancers-13-06312-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f06/8699328/cd615405d7f2/cancers-13-06312-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f06/8699328/cccb65af7c8d/cancers-13-06312-g004.jpg

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