Rapid evolution is ubiquitous in nature in response to anthropogenic disturbances and changes. We will briefly review some of this quite broadly. Nowhere is this more evident, replicated and accessible to study than in cancer. Curiously cancer has been late - relative to fisheries, antibiotic resistance, pest management and evolution in human dominated landscapes - in recognizing the need for evolutionarily informed management strategies. The speed of evolution matters. Here, we employed game-theoretic modelling to compare time to progression with continuous maximum tolerable dose to that of adaptive therapy where treatment is discontinued when the cancer cells' population gets below half of its initial size and re-administered when the cancer cells recover, forming cycles with and without treatment. We show that the success of adaptive therapy relative to continuous maximum tolerable dose therapy is much higher if the population of cancer cells is defined by only two cell types (sensitive versus resistant or "polymorphic"). Additionally, the relative increase in time to progression increases with the speed of evolution. These results hold with and without cost of resistance in cancer cells. On the other hand, when treatment-induced resistance is modeled as a quantitative trait in a monomorphic cancer population, when evolution is rapid, there is no advantage to the adaptive therapy as there is insufficient initial response to treatment in cancer cells, who evolve resistance too quickly. Our study emphasizes how cancer provides a unique system for studying rapid evolutionary changes within tumor ecosystems in response to human interventions and progressive diseases; and allows us to contrast and compare this system to other human managed or dominated systems in nature.

中文翻译：

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癌症治疗诱导抗性的进化动力学有助于理解自然系统的快速进化

响应人为干扰和变化的快速进化在自然界中无处不在。我们将非常广泛地简要回顾其中的一些内容。没有比癌症更明显、更容易复制和更易于研究的地方了。奇怪的是，癌症已经晚了——相对于渔业、抗生素耐药性、害虫管理和人类主导景观的进化——认识到需要进化知情的管理策略。进化的速度很重要。在这里，我们采用博弈论模型将持续最大耐受剂量的进展时间与适应性疗法进行比较，适应性疗法在癌细胞数量低于其初始大小的一半时停止治疗，并在癌细胞恢复时重新给药，有和没有处理的形成循环。我们表明，如果癌细胞群仅由两种细胞类型（敏感与抗性或“多态性”）定义，则适应性治疗相对于连续最大耐受剂量治疗的成功率要高得多。此外，进展时间的相对增加随着进化速度的增加而增加。这些结果在有和没有癌细胞抗性成本的情况下都成立。另一方面，当治疗诱导的耐药性被建模为单态性癌症群体中的数量性状时，当进化迅速时，适应性疗法没有优势，因为癌细胞对治疗的初始反应不足，从而进化出耐药性太快了。我们的研究强调了癌症如何提供一个独特的系统来研究肿瘤生态系统内响应人类干预和进行性疾病的快速进化变化；并允许我们将这个系统与自然界中其他人类管理或支配的系统进行对比和比较。