Evolution Game Theory Modeling of Tumor Dormancy

该项目的PI开发了一种独特的体外技术，可以为研究不同细胞之间的相互作用提供一个真实的肿瘤样环境。人们既可以研究不同的癌细胞，也可以研究癌细胞与器官中其他细胞的相互作用。然而，如果没有一个强大的量化模型来指导我们理解这些细胞群体如何随着时间的变化，我们就无法定量地了解细胞群体的进展，也无法预测癌症的演变。PI将使用复杂的进化博弈论模型来捕捉在实验中观察到的复杂动态。目前，无法预测从诊断到危险评估到休眠结束出现的路径，该项目将发展对如何跟踪癌症不同阶段的理解。该项目将皮埃尔？S技术与物理学家开发的新的显微成像方法相结合，可以用于监测肿瘤的休眠时间，开出依赖时间的治疗方案，并预测癌症从休眠状态中出现的情况。这个急切的项目将解决在零散的、局部相互作用的随机系统中结合复杂的、现实的博弈论的难题，并将其应用于旨在模拟实际肿瘤环境的微制造技术。这个模型原则上消除了导致休眠的常微分方程式中的奇点，PI将用应力下癌细胞活力的实验重新出现来测试该模型。该项目由物理学部的生命系统物理学项目和分子和细胞生物科学部的分子生物物理组共同支持。

The PI of this project has developed a unique in vitro technology which can provide a realistic tumor-like environment to study the interactions between different cells. One can study both different cancer cells and cancer cells interacting with other cells in the organ. However, without a strong quantitative model capable of guiding our understanding of how these cell population change with time, we cannot quantitatively understand the progression of the cell populations nor make predictions of the cancer evolution. The PI will use sophisticated evolutionary game theory models to capture the complex dynamics observed in the experiments. Currently the path from diagnosis through estimation of hazards to emergence of the end of dormancy cannot be predicted and this project will develop understanding of how to follow different stages of cancer. Combining the PI?s technology with new micro-imaging modalities that have been developed by physicists, this project can be used to monitor the duration of dormancy in tumors, prescribe time-dependent therapies, and predict cancer emergence from dormancy. This EAGER project will tackle the difficult problem of combining sophisticated, realistic game theory in patchy, locally interacting and stochastic systems and apply it to a micro-fabricated technology designed to mimic the actual tumor environment. The singularities in the ordinary differential equations that gave rise to dormancy are in principle removed by this modeling, and the PI will test the modeling with experimental re-emergence of cancer cell viability under stress. This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences.