Cancer Therapy Design Based on Pathway Information

摘要目的：该项目的主要目标是开发一种更系统的癌症治疗方法，以提高成功率。 目前的癌症疗法有两个主要缺点：（i）它们没有考虑到任何两个个体之间存在的遗传差异，即使他们非常健康;（ii）它们无法精确定位导致特定患者癌症的细胞信号传导中的精确故障。 智力优势：多细胞生物体（如人类）中的细胞数量受到非常严格的控制，在正常情况下，新细胞产生和细胞死亡之间存在某种平衡。 粗略地说，当细胞数量控制系统出现故障而导致细胞过度分裂或细胞死亡减少时，就会产生癌症。 癌症治疗之所以如此困难，是因为这种故障可能以许多不同的方式发生在许多不同的位置。该项目旨在利用生物学文献中的先验信息将正常细胞信号网络建模为数字电路，其在可能发生故障时的输出可用于精确定位故障位置并相应地定制治疗。理论工作将得到实验验证。更广泛的影响：由于该项目的研究专门针对癌症治疗，因此其最终挽救人类生命的潜在社会效益可能是巨大的。此外，这里开发的方法有可能影响其他领域，如毒理学研究，重点是细胞对不同压力的反应。将尽一切努力确保该项目的好处惠及广大受众，包括少数民族和国内学生。此外，该项目的成果将导致出版一本新书。

ABSTRACTObjective: The main objective of this project is to develop a more systematic approach towards cancer treatment in order to a better success rate. Current cancer therapies suffer from two main drawbacks: (i) they do not take into account the genetic differences that exist between any two individuals, even if they are perfectly healthy; and (ii) they fail to pinpoint the precise malfunctioning in the cellular signaling that has led to the cancer seen in a particular patient. Intellectual Merit: The number of cells in a multi-cellular organism such as a human being is under very tight control and, under normal circumstances, there is some kind of a balance between new cell production and cell death. Roughly speaking, cancer results when there is excessive cell division or reduced cell death due to some malfunctioning in the cell number control system. What makes cancer therapy so difficult is that this malfunctioning can happen in many different ways and at many different locations. This project seeks to use prior information from the biological literature to model the normal cell signaling network as a digital circuit, whose output upon a possible breakdown can be used to pinpoint the precise breakdown location and accordingly tailor the therapy. The theoretical work will be experimentally validated. Broader Impacts: Since the research in this project specifically targets cancer therapy, its potential societal benefits in terms of ultimately saving human lives could be enormous. In addition, the methods developed here have the potential to impact other areas such as toxicological studies focusing on cellular response to different stresses. Every effort will be made to ensure that the benefits of the project reach a wide audience, including minorities and domestic students. In addition, the results of this project will lead to the publication of a new book.