Evolution Game Theory Modeling of Tumor Dormancy

该项目的PI开发了一种独特的体外技术，可以提供一个真实的肿瘤样环境来研究不同细胞之间的相互作用。我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定量模型来指导我们了解这些细胞群是如何随时间变化的，我们就无法定量地了解细胞群的进展，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实验中观察到的复杂动态。目前，从诊断到估计危害到出现休眠结束的路径无法预测，该项目将发展对如何跟踪癌症不同阶段的理解。结合PI？利用物理学家开发的新型微成像技术，该项目可用于监测肿瘤的休眠时间，开出时间依赖性治疗方案，并预测癌症从休眠中出现。这个EAGER项目将解决将复杂的、现实的博弈论与局部相互作用和随机系统相结合的难题，并将其应用于模拟实际肿瘤环境的微制造技术。该模型原则上消除了常微分方程中导致休眠的奇异性，PI将通过在压力下重新出现癌细胞活力的实验来测试该模型。该项目由物理系的生命系统物理学项目和分子与细胞生物科学系的分子生物物理集群共同支持。

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.