Department of Computer Science, University of Oxford, Oxford, UK.
Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, USA.
Nat Ecol Evol. 2019 Mar;3(3):450-456. doi: 10.1038/s41559-018-0768-z. Epub 2019 Feb 18.
Heterogeneity in strategies for survival and proliferation among the cells that constitute a tumour is a driving force behind the evolution of resistance to cancer therapy. The rules mapping the tumour's strategy distribution to the fitness of individual strategies can be represented as an evolutionary game. We develop a game assay to measure effective evolutionary games in co-cultures of non-small cell lung cancer cells that are sensitive and resistant to the anaplastic lymphoma kinase inhibitor alectinib. The games are not only quantitatively different between different environments, but targeted therapy and cancer-associated fibroblasts qualitatively switch the type of game being played by the in vitro population from Leader to Deadlock. This observation provides empirical confirmation of a central theoretical postulate of evolutionary game theory in oncology: we can treat not only the player, but also the game. Although we concentrate on measuring games played by cancer cells, the measurement methodology we develop can be used to advance the study of games in other microscopic systems by providing a quantitative description of non-cell-autonomous effects.
肿瘤细胞中存活和增殖策略的异质性是癌症治疗耐药性演变的驱动力。将肿瘤的策略分布映射到个体策略适应性的规则可以表示为进化博弈。我们开发了一种博弈测定法，以测量对间变性淋巴瘤激酶抑制剂阿来替尼敏感和耐药的非小细胞肺癌细胞共培养物中的有效进化博弈。这些博弈不仅在不同环境之间存在定量差异，而且靶向治疗和癌症相关成纤维细胞还会使体外群体中正在进行的博弈类型从主导策略转变为僵局策略。这一观察结果为肿瘤进化博弈理论的一个核心理论假设提供了经验证据：我们不仅可以治疗参与者，还可以治疗游戏。虽然我们专注于测量癌细胞进行的博弈，但我们开发的测量方法可用于通过提供非细胞自主效应的定量描述来推进其他微观系统中博弈的研究。
