Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics
Abstract Cellular senescence is a double-edged sword in cancer biology, functioning as both a tumor-suppressive mechanism and a driver of malignancy. Initially, senescence acts as a protective barrier by arresting the proliferation of damaged or oncogene-expressing cells via pathways such as oncogen...
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| Format: | Article |
| Language: | English |
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BMC
2025-08-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-025-02419-2 |
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| author | Tiejun Feng Fuda Xie Leo M.Y. Lee Zhiqiang Lin Yifan Tu Yang Lyu Peiyao Yu Jialin Wu Bonan Chen Ge Zhang Gary M.K. Tse Ka Fai To Wei Kang |
| author_facet | Tiejun Feng Fuda Xie Leo M.Y. Lee Zhiqiang Lin Yifan Tu Yang Lyu Peiyao Yu Jialin Wu Bonan Chen Ge Zhang Gary M.K. Tse Ka Fai To Wei Kang |
| author_sort | Tiejun Feng |
| collection | DOAJ |
| description | Abstract Cellular senescence is a double-edged sword in cancer biology, functioning as both a tumor-suppressive mechanism and a driver of malignancy. Initially, senescence acts as a protective barrier by arresting the proliferation of damaged or oncogene-expressing cells via pathways such as oncogene-induced senescence and the DNA damage response. However, persistent senescence-associated secretory phenotype and metabolic reprogramming in senescent cells create a pro-inflammatory, immunosuppressive tumor microenvironment, fueling cancer progression, therapy resistance, and metastasis. This comprehensive review systematically examines the molecular mechanisms of senescence across diverse cancers, spanning digestive, reproductive, urinary, respiratory, nervous, hematologic, endocrine, and integumentary systems, and elucidates its context-dependent roles in tumor suppression and promotion. We highlight groundbreaking therapeutic innovations, including precision senolytics, senomorphics, and combinatorial strategies integrating immunotherapy, metabolic interventions, and epigenetic modulators. The review also addresses microenvironment remodeling and cutting-edge technologies for dissecting senescence heterogeneity, epigenetic clocks for biological age prediction, and microbiome engineering to modulate senescence. Despite their promise, challenges such as off-target effects, biomarker limitations, and cellular heterogeneity underscore the need for precision medicine approaches. Finally, we propose future directions to harness senescence as a dynamic therapeutic target, offering transformative potential for cancer treatment. |
| format | Article |
| id | doaj-art-4db34aa74fff40769484b416cfcd74c6 |
| institution | Kabale University |
| issn | 1476-4598 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-4db34aa74fff40769484b416cfcd74c62025-08-20T03:45:48ZengBMCMolecular Cancer1476-45982025-08-0124113410.1186/s12943-025-02419-2Cellular senescence in cancer: from mechanism paradoxes to precision therapeuticsTiejun Feng0Fuda Xie1Leo M.Y. Lee2Zhiqiang Lin3Yifan Tu4Yang Lyu5Peiyao Yu6Jialin Wu7Bonan Chen8Ge Zhang9Gary M.K. Tse10Ka Fai To11Wei Kang12Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Sir Y.K. Pao Cancer Center, The Chinese University of Hong KongDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Sir Y.K. Pao Cancer Center, The Chinese University of Hong KongDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic UniversityNational Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Southern University of Science and TechnologyDepartment of Obstetrics and Gynaecology, The Chinese University of Hong KongDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Sir Y.K. Pao Cancer Center, The Chinese University of Hong KongDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Sir Y.K. Pao Cancer Center, The Chinese University of Hong KongDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Sir Y.K. Pao Cancer Center, The Chinese University of Hong KongDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Sir Y.K. Pao Cancer Center, The Chinese University of Hong KongLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist UniversityDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Sir Y.K. Pao Cancer Center, The Chinese University of Hong KongDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Sir Y.K. Pao Cancer Center, The Chinese University of Hong KongDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, Sir Y.K. Pao Cancer Center, The Chinese University of Hong KongAbstract Cellular senescence is a double-edged sword in cancer biology, functioning as both a tumor-suppressive mechanism and a driver of malignancy. Initially, senescence acts as a protective barrier by arresting the proliferation of damaged or oncogene-expressing cells via pathways such as oncogene-induced senescence and the DNA damage response. However, persistent senescence-associated secretory phenotype and metabolic reprogramming in senescent cells create a pro-inflammatory, immunosuppressive tumor microenvironment, fueling cancer progression, therapy resistance, and metastasis. This comprehensive review systematically examines the molecular mechanisms of senescence across diverse cancers, spanning digestive, reproductive, urinary, respiratory, nervous, hematologic, endocrine, and integumentary systems, and elucidates its context-dependent roles in tumor suppression and promotion. We highlight groundbreaking therapeutic innovations, including precision senolytics, senomorphics, and combinatorial strategies integrating immunotherapy, metabolic interventions, and epigenetic modulators. The review also addresses microenvironment remodeling and cutting-edge technologies for dissecting senescence heterogeneity, epigenetic clocks for biological age prediction, and microbiome engineering to modulate senescence. Despite their promise, challenges such as off-target effects, biomarker limitations, and cellular heterogeneity underscore the need for precision medicine approaches. Finally, we propose future directions to harness senescence as a dynamic therapeutic target, offering transformative potential for cancer treatment.https://doi.org/10.1186/s12943-025-02419-2SenescenceCancerTherapeutic innovation |
| spellingShingle | Tiejun Feng Fuda Xie Leo M.Y. Lee Zhiqiang Lin Yifan Tu Yang Lyu Peiyao Yu Jialin Wu Bonan Chen Ge Zhang Gary M.K. Tse Ka Fai To Wei Kang Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics Molecular Cancer Senescence Cancer Therapeutic innovation |
| title | Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics |
| title_full | Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics |
| title_fullStr | Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics |
| title_full_unstemmed | Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics |
| title_short | Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics |
| title_sort | cellular senescence in cancer from mechanism paradoxes to precision therapeutics |
| topic | Senescence Cancer Therapeutic innovation |
| url | https://doi.org/10.1186/s12943-025-02419-2 |
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