Combination of radiation with multi-target molecular the

生长因子受体在许多癌症中过度表达，它们的存在与预后不良有关。生长因子信号通路的激活会增加细胞的增殖、活力以及对化疗和放射治疗的抵抗力。最近的研究表明，肿瘤细胞对旨在阻断单个生长因子信号通路的治疗的耐药性可能是由与另一种生长因子通路的串扰引起的。例如，IGF途径的激活干扰了抗EGF途径的治疗。直到最近，适当的软件工具和足够的计算机能力才出现，允许对像EGF/IGF途径这样复杂的信号通路进行定量的计算探索。生长因子信号系统的并发症使得靶向治疗的经验方法非常低效。我们建议在现有文献数据的基础上建立一个详细的信号通路计算模型，并使用定量生物化学实验验证其准确性。该模型将允许模拟细胞对生长因子的反应，并(在电子计算机中)探索旨在选择性阻断这些途径的可能的治疗干预措施，并为优化肿瘤过度表达生长因子受体(如IGF和EGF受体家族)的分子治疗提供手段。

Growth factor receptors are overexpressed in many cancers and their presence correlates with poor prognosis. Activation of growth factors signaling pathways results in increased proliferation, motility and resistance to chemo - and radiation therapies. It has been shown recently that the resistance of tumor cells to therapy aimed at blocking individual growth factor signaling pathways may be caused by cross-talk with another growth factor pathway. For example, activation of IGF pathway interferes with anti-EGF pathway therapy. Only very recently, appropriate software tools and sufficient computer power have become available that allow a quantitative computational exploration of signaling pathways as complex as the EGF/IGF pathway. Complication of the growth factor signaling system makes the empirical approach to targeted therapy quite inefficient. We propose to create a detailed computational model signaling pathways based on available literature data and experimentally verify its accuracy using quantitative biochemistry. The model will allow simulation of cellular response to growth factors and computational (in silico) exploration of possible therapeutic interventions aiming at selective blocking of these pathways and provide means for optimization of molecular therapy for tumors overexpressing growth factor receptors, e.g. IGF and EGF receptor families.