肿瘤细胞亚群之间的合作导致肿瘤内异质性
Cooperation among tumor cell subpopulations leads to intratumor heterogeneity
摘要：
异型增生是所有癌症的标志。肿瘤异质性存在于不同的水平-患者间、患者内和肿瘤内异质性。所有这些都对临床治疗提出了挑战。后两种情况也会增加产生耐药性的风险。尽管肿瘤异质性的存在已经被认识了两个世纪，但对其起源的清楚理解仍然是难以捉摸的，特别是在肿瘤内异质性（ITH）水平上。单个肿瘤内不同亚群的共存已被证明在癌发生的所有阶段发挥关键作用。在这里，使用进化博弈论和公共产品博弈的概念，经常调用的背景下的悲剧公地，我们探讨如何亚克隆种群之间的相互作用影响ITH的建立。通过使用一个进化模型，它统一了几个实验结果在不同的癌症类型，我们开发了定量的理论模型，用于解释数据从{ \it在体外}实验涉及胰腺癌以及{ \it体内}数据在多形性胶质母细胞瘤。这种物理和数学模型补充了实验研究，并乐观地为癌症患者设计有效的治疗方法提供了新的思路。
英文摘要：
Heterogeneity is a hallmark of all cancers. Tumor heterogeneity is found at different levels -- interpatient, intrapatient, and intratumor heterogeneity. All of them pose challenges for clinical treatments. The latter two scenarios can also increase the risk of developing drug resistance. Although the existence of tumor heterogeneity has been known for two centuries, a clear understanding of its origin is still elusive, especially at the level of intratumor heterogeneity (ITH). The coexistence of different subpopulations within a single tumor has been shown to play crucial roles during all stages of carcinogenesis. Here, using concepts from evolutionary game theory and public goods game, often invoked in the context of the tragedy of commons, we explore how the interactions among subclone populations influence the establishment of ITH. By using an evolutionary model, which unifies several experimental results in distinct cancer types, we develop quantitative theoretical models for explaining data from {\it in vitro} experiments involving pancreatic cancer as well as {\it vivo} data in glioblastoma multiforme. Such physical and mathematical models complement experimental studies, and could optimistically also provide new ideas for the design of efficacious therapies for cancer patients.
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