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揭示癌症中的衰老:机制复杂性与治疗机遇

英文原题:Unraveling senescence in cancer: mechanistic complexities and therapeutic opportunities.

查看英文原题

Unraveling senescence in cancer: mechanistic complexities and therapeutic opportunities.

PubMed 2025/05/30(内容时间) Mol Biol Rep Q3 · IF 3.2(JCR 2025)

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中文摘要

衰老是一个关键的细胞过程,在发育、免疫调节、组织修复和衰老中同样发挥重要作用,由端粒缩短、癌基因激活和 DNA 损伤等应激因素触发。衰老以独特的形态学和分子特征为标志,已知通过不可逆的细胞周期阻滞充当肿瘤抑制机制。然而,新兴研究揭示了一个悖论:癌细胞中持续的衰老可通过衰老相关分泌表型驱动肿瘤发生,促进增殖、侵袭和转移。这篇综合性综述阐明了衰老在诱导生长阻滞、增强免疫监视以及有利地调节肿瘤微环境以抑制癌症进展方面的分子复杂性。此外,它还审视了常规疗法的衰老诱导效应,并探索了新兴疗法的潜力,包括靶向治疗和CAR-T 细胞疗法。本综述还强调了衰老治疗策略在选择性靶向衰老细胞以改善治疗结局方面的前景。它讨论了机器学习工具在生物标志物发现和患者分层方面的创新性整合,为改善癌症治疗疗效提供了一种变革性方法。

展开英文摘要原文

Senescence is a pivotal cellular process, which also plays a major role in development, immune regulation, tissue repair, and aging, triggered by stressors such as telomere shortening, oncogene activation, and DNA damage. Characterized by distinct morphological and molecular features, senescence is known to act as a tumor suppressive mechanism through irreversible cell cycle arrest.

However, emerging studies reveal a paradox: prolonged senescence in cancer cells can drive tumorigenesis via the senescence-associated secretory phenotype, promoting proliferation, invasion, and metastasis. This comprehensive review elucidates the molecular intricacies of senescence to induce growth arrest, enhance immune surveillance, and favorably modulate the tumor microenvironment to inhibit cancer progression.

Additionally, it examines the senescence-inducing effects of conventional therapies and explores the potential of emerging therapies, including targeted therapies and chimeric antigen receptor T cell therapy. The present review also highlights the promise of senotherapeutic strategies in selectively targeting senescent cells to improve therapeutic outcomes. It discusses the innovative integration of machine learning tools for biomarker discovery and patient stratification offering a transformative approach to improve cancer treatment efficacy.

论文信息

作者
Tiwari P、Shukla SK、Rastogi Verma S
第一作者单位
Department of Biotechnology, Delhi Technological University, Delhi, 110042, India.India
通讯作者单位
Department of Biotechnology, Delhi Technological University, Delhi, 110042, India. smitar@dtu.ac.in.India
文献类型
综述
期刊
Molecular biology reports2025 May 30
原文标识
PubMed 40445455 · DOI 10.1007/s11033-025-10630-z