Wang Zhihui, Bordas Veronika, Sagotsky Jonathan, Deisboeck Thomas S
Complex Biosystems Modeling Laboratory, Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital-East, 13th Street, Charlestown, MA 02129, USA.
Math Med Biol. 2012 Mar;29(1):95-108. doi: 10.1093/imammb/dqq023. Epub 2010 Dec 8.
Applying a previously developed non-small cell lung cancer model, we assess 'cross-scale' the therapeutic efficacy of targeting a variety of molecular components of the epidermal growth factor receptor (EGFR) signalling pathway. Simulation of therapeutic inhibition and amplification allows for the ranking of the implemented downstream EGFR signalling molecules according to their therapeutic values or indices. Analysis identifies mitogen-activated protein kinase and extracellular signal-regulated kinase as top therapeutic targets for both inhibition and amplification-based treatment regimen but indicates that combined parameter perturbations do not necessarily improve the therapeutic effect of the separate parameter treatments as much as might be expected. Potential future strategies using this in silico model to tailor molecular treatment regimen are discussed.
应用先前开发的非小细胞肺癌模型，我们“跨尺度”评估了靶向表皮生长因子受体（EGFR）信号通路多种分子成分的治疗效果。治疗抑制和扩增的模拟允许根据其治疗价值或指标对所实施的下游EGFR信号分子进行排名。分析确定丝裂原活化蛋白激酶和细胞外信号调节激酶是基于抑制和扩增的治疗方案的首要治疗靶点，但表明联合参数扰动不一定能如预期那样显著提高单独参数治疗的治疗效果。讨论了使用这种计算机模拟模型定制分子治疗方案的潜在未来策略。
