癌症生物标志物可提供关于癌症进展特征和程度的信息，帮助临床决策。然而，它们还可以在肿瘤发生中起到功能性作用，从促进转移和诱导血管生成到促进对化疗的耐药性。由此产生的进化过程可能会偏差癌症进展估计，并导致次优的治疗决策。我们建立了一个细胞间竞争的进化博弈模型，研究了不同水平生物标志物产生的癌细胞之间的竞争。我们在现有的博弈基础上设计和模拟治疗方案，并研究了人群和生物标志物的动态。以总生物标志物作为种群大小的代理通常会低估化疗的有效性，并高估靶向治疗的有效性。如果生物标志物的产生促进了耐药性，并存在一种针对该生物标志物的靶向治疗，这种动态可以用来建立进化陷阱。化疗选择高生物标志物产生的癌细胞种群后，靶向治疗可能对癌症消灭非常有效。与根据癌症当前生物标志物水平和种群大小使用最有效的治疗方法不同，当目标是消灭时，“超射”并利用进化陷阱更加有效。增加细胞间竞争，受生物标志物水平影响，可以帮助预设和设定这些陷阱。功能性生物标志物的进化放大了在设计治疗方案时使用总生物标志物水平作为肿瘤大小测量的局限性。在存在针对该生物标志物的靶向治疗时，进化启发的治疗策略可能非常有效。© 2023 作者。由牛津大学出版社代表进化、医学和公共卫生基金会发表。

Cancer biomarkers provide information on the characteristics and extent of cancer progression and help inform clinical decision-making. However, they can also play functional roles in oncogenesis, from enabling metastases and inducing angiogenesis to promoting resistance to chemotherapy. The resulting evolution could bias estimates of cancer progression and lead to suboptimal treatment decisions.We create an evolutionary game theoretic model of cell-cell competition among cancer cells with different levels of biomarker production. We design and simulate therapies on top of this pre-existing game and examine population and biomarker dynamics.Using total biomarker as a proxy for population size generally underestimates chemotherapy efficacy and overestimates targeted therapy efficacy. If biomarker production promotes resistance and a targeted therapy against the biomarker exists, this dynamic can be used to set an evolutionary trap. After chemotherapy selects for a high biomarker-producing cancer cell population, targeted therapy could be highly effective for cancer extinction. Rather than using the most effective therapy given the cancer's current biomarker level and population size, it is more effective to 'overshoot' and utilize an evolutionary trap when the aim is extinction. Increasing cell-cell competition, as influenced by biomarker levels, can help prime and set these traps.Evolution of functional biomarkers amplify the limitations of using total biomarker levels as a measure of tumor size when designing therapeutic protocols. Evolutionarily enlightened therapeutic strategies may be highly effective, assuming a targeted therapy against the biomarker is available.© The Author(s) 2023. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.