Senescence-associated secretory phenotype in lung cancer: remodeling the tumor microenvironment for metastasis and immune suppression

被引：0

作者：

Chen, Chen ^{[1
]}

Chen, Ji ^{[1
]}

Zhang, Yanling ^{[1
]}

Zhang, Qijun ^{[2
]}

Shi, Haixia ^{[3
]}

机构：

[1] Shanghai Pudong New Area Pulm Hosp, Dept Tradit Chinese Med TCM, Shanghai, Peoples R China

[2] Integrated Tradit Chinese & Western Med Hosp Shang, Dept Oncol, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Tradit Chinese Med, Sch Med, Shanghai, Peoples R China

来源：

FRONTIERS IN ONCOLOGY | 2025年 / 15卷

关键词：

cellular senescence; lung cancer; SASP; therapy resistance; precision medicine; CELLULAR SENESCENCE; IONIZING-RADIATION; SIGNALING PATHWAY; PD-1; BLOCKADE; CELLS; ADENOCARCINOMA; SURVIVAL; ATM; INHIBITORS; DEPLETION;

D O I：

10.3389/fonc.2025.1605085

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cellular senescence exerts dual roles in lung cancer pathogenesis: initially suppressing tumorigenesis via p53/p21/p16-mediated cell cycle arrest, but promoting malignancy through the senescence-associated secretory phenotype (SASP). SASP secretes cytokines, proteases, and growth factors, reshaping the tumor microenvironment (TME) to drive immune evasion, metastasis, and therapy resistance. NF-kappa B activation induces APOBEC3B mutagenesis and PD-L1 overexpression, while mTOR signaling enhances glycolysis and OXPHOS to fuel tumor growth. Clinically, telomere attrition, p16/p21 expression, and SASP components serve as prognostic biomarkers. Therapeutic strategies target senescent cells and SASP. Future directions focus on single-cell multi-omics to decode senescence heterogeneity, spatially controlled drug delivery, and therapies targeting senescence-immune-metabolic crosstalk. By unraveling senescence's dual regulatory mechanisms, this review highlights precision approaches to overcome resistance and improve lung cancer outcomes.

引用

页数：13

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