Combination of radiation with multi-target molecular the

辐射与多靶分子的结合

• 批准号: 7291941
• 负责人: jacek capala
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7291941
• 关键词: Combination; radiation; multi; target; molecular

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.

生长因子受体在大多数癌症中过度表达，它们的存在与预后不良有关。EGF-和IGF-信号通路的激活导致细胞增殖、活力增强以及对化疗和放射治疗的抵抗力增强。研究表明，肿瘤细胞对基于阻断单个生长因子信号通路的靶向治疗的耐药性可能是与另一种生长因子信号通路的串扰所致。例如，IGFR途径的激活干扰了抗EGF途径的治疗。为了增加肿瘤对放射的敏感性，我们将探索一种同时阻断EGF和IGF信号通路的多靶点方法，方法如下：1)在计算机、体外和体内实验中，同时阻断不同步骤的EGF和IGF信号通路对肿瘤和正常组织的影响；2)研究阻断相关通路对放射治疗结果的影响，以确定临床试验的最佳组合。3)体内可视化信号成分，以监测治疗对其活性的影响。