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模拟癌症进化轨迹的衰老依赖性。

Modelling the ageing dependence of cancer evolutionary trajectories.

作者信息

Henry Curtis J, DeGregori James

机构信息

The Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

The Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

出版信息

Nat Rev Cancer. 2025 Jul 10. doi: 10.1038/s41568-025-00838-3.

Abstract

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

衰老 是癌症发生最重要的单一预后因素。尽管有这一认识,但癌症实验模型历来都没有考虑到年龄对癌症起始、进展和治疗结果的影响。衰老与其他生活方式因素相互作用,包括吸烟、肥胖和身体活动,但在实验模型中很少研究这些交叉点。鉴于癌症相关死亡率随年龄增长而增加,癌症研究中越来越强调对与衰老相关的突变和微环境变化进行建模。在本综述中,我们就技术进步和实验策略提供指导,这些进步和策略提高了我们对衰老如何影响癌症演变各个阶段进行建模的能力,从突变驱动的克隆扩增到癌前病变,再到进展为更恶性的表型和转移,以及对治疗的反应。我们讨论了所使用方法和模型的优缺点。更广泛地采用适合年龄的癌症模型将有助于开发改进的方法,用于人类癌症的检测、预防和治疗干预。

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