文章：

癌症进化轨迹的衰老依赖性建模

Modelling the ageing dependence of cancer evolutionary trajectories

原文发布日期：2025-07-10

DOI: 10.1038/s41568-025-00838-3

类型: Review Article

开放获取: 否

英文摘要：

Ageing is the single most important prognostic factor for cancer development. Despite this knowledge, experimental models of cancer have historically omitted incorporating the impact of age on cancer initiation, progression and treatment outcomes. Ageing interacts with other lifestyle factors, including cigarette smoking, obesity and physical activity, but these intersections are rarely studied in experimental models. Given that cancer-related mortality rates increase with age, there is a growing emphasis on modelling ageing-associated mutational and microenvironmental changes in cancer research. In this Review, we provide guidance on the technological advancements and experimental strategies that have increased our ability to model how ageing impacts various stages of cancer evolution, from mutation-driven clonal expansions, to pre-malignant lesions, and then to progression to more malignant phenotypes and metastasis, and responses to therapies. We discuss the benefits and limitations of methods and models used. The wider adoption of age-appropriate models of cancer will enable the development of improved approaches for the detection, prevention and therapeutic intervention of human cancers.

摘要翻译： 

衰老是癌症发生最重要的预后因素。尽管已知这一事实，癌症的实验模型历来忽略了年龄对癌症发生、进展及治疗结果的影响。衰老与吸烟、肥胖和身体活动等其他生活方式因素存在交互作用，但实验模型很少研究这些交叉影响。鉴于癌症相关死亡率随年龄增长而上升，癌症研究中对衰老相关突变和微环境变化的建模日益受到重视。本综述针对技术进步和实验策略提供指导，这些进展增强了我们模拟衰老如何影响癌症演化各阶段的能力——从突变驱动的克隆扩张，到癌前病变，再到恶性表型进展与转移，以及对治疗的反应。我们讨论了所用方法和模型的优势与局限性。更广泛采用适龄癌症模型将有助于开发改进的癌症检测、预防和治疗干预策略。

原文链接：

Modelling the ageing dependence of cancer evolutionary trajectories