Combination of radiation with multi-target molecular the

放射与多目标分子的结合

• 批准号: 7338739
• 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/7338739
• 关键词: Combination; radiation; multi; target; molecular

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.

生长因子受体在许多癌症中过表达，它们的存在与不良预后相关。生长因子信号通路的激活导致增殖、运动性和对化疗和放疗的抗性增加。最近已经表明，肿瘤细胞对旨在阻断个体生长因子信号传导途径的治疗的抗性可能是由与另一种生长因子途径的串扰引起的。例如，IGF途径的激活干扰抗EGF途径治疗。直到最近，适当的软件工具和足够的计算机能力已经成为可用的，允许定量计算探索的信号通路复杂的EGF/IGF途径。生长因子信号系统的复杂性使得靶向治疗的经验方法相当低效。我们建议创建一个详细的计算模型信号通路的基础上，现有的文献数据和实验验证其准确性，使用定量生物化学。该模型将允许模拟细胞对生长因子的反应，并通过计算机（in silico）探索旨在选择性阻断这些途径的可能的治疗干预，并提供优化过表达生长因子受体（如IGF和EGF受体家族）的肿瘤分子治疗的方法。