Multiscale Tumor Model for Cancer Treatment Prototyping

描述（由申请人提供）： 癌症是美国第二大死亡原因，尽管该领域的研究非常活跃，但与癌症相关的死亡人数在过去十年中并没有显著下降。与开发有效治疗相关的主要问题是在实验室或临床环境中监测体内癌症行为所需的长时间尺度。目前理论生物学的进步创造了一种独特的可能性，可以使用基于计算机的数值模拟进行许多冗长的计算机研究。我们建议开发高保真的软件工具，使这样的模拟。肿瘤控制的关键之一是通过血管生成实现肿瘤血管化。我们已经在I期研究中证明了开发能够模拟与血管/癌症动力学相关的显著特征的计算机软件的可行性。我们已经证明，我们不仅可以模拟计算功能血管的形成，而且还可以模拟血管生成抑制剂对发育中的血管系统的影响。第二阶段的研究将是CFDRC和范德比尔特大学的合作努力。现有的代码功能将通过开发新的和合并现有的模型，使用分层代码结构，导致在一个灵活的配方，允许更新/包括新的生化动力学模型，因为它们变得可用。开发的软件将被广泛验证对体内实验的数据由我们的范德比尔特的同事。这项工作提供了一种新的和高度创新的方法，能够预测生理上正确的脉管系统，从而允许模拟血液运输和治疗肿瘤。使用这项技术，研究和开发癌症治疗所需的时间可以从几个月（目前的情况）减少到几小时或几天。该软件还将允许对体内不实用的治疗进行计算机模拟研究。

DESCRIPTION (provided by applicant): Cancer is the second leading cause of death in the U.S. Despite very active research in the area, the number of deaths related to cancer has not fallen significantly in the past decade. A major problem associated with the development of effective treatments is the long time scales required for monitoring of in-vivo cancer behavior in a laboratory or clinical setting. Current advancements in theoretical biology have created a unique possibility to conduct many of the lengthy studies in-silico using computer-based numerical simulations. We propose to develop high-fidelity software tools to enable such simulations. One of the keys to tumor control is tumor vascularization through angiogenesis. We have demonstrated in Phase I research the feasibility of developing computer software capable of modeling the salient features associated with angio/cancer dynamics. We have shown that we can simulate not only the formation of computationally functional blood vessels, but also the effects on angiogenesis inhibitors on the developing vasculature. Phase II research will be a collaborative effort of CFDRC and Vanderbilt University. The existing code capabilities will be further extended by developing new and incorporating existing models using a hierarchical code structure that results in a flexible formulation that allows updating/inclusion of new biochemical dynamics models as they become available. The developed software will be extensively validated against data from in-vivo experiments performed by our Vanderbilt colleagues. This work provides a new and highly innovative method capable of predicting physiologically correct vasculature, thereby permitting the simulation of blood transport and therapeutics to the tumor. Using this technology, the time required in the studies and development of cancer treatments can be potentially reduced from months (as is currently the case) to hours or days. The software will also allow in-silico investigation of treatments that are not practical in-vivo.