Combination of radiation with multi-target molecular the

生长因子受体在大多数癌症中过度表达，其存在与不良预后相关。EGF-和igf -信号通路的激活导致细胞增殖、运动和对化疗和放疗的抗性增加。已有研究表明，肿瘤细胞对基于阻断个体生长因子信号通路的靶向治疗产生耐药性可能是由于与另一种生长因子通路的串扰引起的。例如，IGFR通路的激活会干扰抗egf通路的治疗。为了提高肿瘤对辐射的敏感性，我们将通过以下方法研究阻断EGF和IGF信号通路的多靶点方法：1)同时阻断EGF和IGF信号通路各步骤对肿瘤和正常组织的影响的硅、体外和体内研究。2)研究阻断相关通路对放疗结果的影响，以确定临床试验的最佳组合。3)体内信号成分可视化，以监测治疗对其活动的影响。

Growth factor receptors are overexpressed in most cancers and their presence correlates with poor prognosis. Activation of EGF- and IGF-signaling pathways results in increased proliferation, motility and resistance to chemo- and radiation therapy. It has been shown that the resistance of tumor cells to targeted therapy based on blocking individual growth factor signaling pathways may be caused by cross-talk with another growth factor pathway. For example, activation of IGFR pathway interferes with anti-EGF pathway therapy. In order to increase tumor sensitivity to radiation, we will investigate a multi-target approach blocking both EGF and IGF pathways by:1) In silico, in vitro and in vivo studies of the effects of simultaneous blockage of various steps of EGF and IGF signaling pathways on tumor and normal tissues.2) Study of the effects of blocking of the relevant pathways bon the outcome of radiotherapy in order to identify optimal combination for clinical trials.3) In vivo visualization of the signaling components to monitor the effects of therapy on their activities.