MINI REVIEW article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1605085
This article is part of the Research TopicFormation of Immunological Niches in Tumor Microenvironments: Mechanisms and Therapeutic PotentialView all 28 articles
Senescence-Associated Secretory Phenotype in Lung Cancer: Remodeling the Tumor Microenvironment for Metastasis and Immune Suppression
Provisionally accepted
- 1Shanghai Pudong New Area Pulmonary Hospital, shanghai, China
- 2Shanghai Minhang District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
- 3Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai Municipality, China
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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-κB 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.
Keywords: cellular senescence, lung cancer, SASP, therapy resistance, precision medicine
Received: 02 Apr 2025; Accepted: 12 May 2025.
Copyright: © 2025 Chen, Chen, Zhang, Zhang and SHI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qijun Zhang, Shanghai Minhang District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
Haixia SHI, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai Municipality, China
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