Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapy
Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME), playing a pivotal role in tumor initiation, progression, and therapeutic resistance. This review explores the dual roles of CAFs in regulating tumor cell senescence and cell death, elucidating their mec...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1635771/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849719384005672960 |
|---|---|
| author | Guixiang Ruan Xiang Wang Huiyi Ou Huiyi Ou Duancheng Guo Duancheng Guo Duancheng Guo |
| author_facet | Guixiang Ruan Xiang Wang Huiyi Ou Huiyi Ou Duancheng Guo Duancheng Guo Duancheng Guo |
| author_sort | Guixiang Ruan |
| collection | DOAJ |
| description | Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME), playing a pivotal role in tumor initiation, progression, and therapeutic resistance. This review explores the dual roles of CAFs in regulating tumor cell senescence and cell death, elucidating their mechanisms in inducing cellular senescence, shaping an immunosuppressive milieu, and modulating cell death pathways. CAFs promote tumor progression by secreting pro-inflammatory factors and extracellular matrix (ECM) components, while also contributing to metabolic reprogramming, immune evasion, and therapy resistance, thereby influencing anti-cancer treatment efficacy. Studies indicate that the heterogeneity and plasticity of CAFs determine their distinct functions across various tumor types. Consequently, precision-targeted therapeutic strategies against CAFs, including the elimination of senescent CAFs, inhibition of the senescence-associated secretory phenotype (SASP), and disruption of CAF-mediated cell death evasion mechanisms, have emerged as promising directions in cancer research. This review provides a comprehensive analysis of CAFs functions and their potential as therapeutic targets, offering valuable insights into the development of novel anti-cancer strategies. |
| format | Article |
| id | doaj-art-fdba13de123c4772bcadb761eebc34bd |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-fdba13de123c4772bcadb761eebc34bd2025-08-20T03:12:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16357711635771Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapyGuixiang Ruan0Xiang Wang1Huiyi Ou2Huiyi Ou3Duancheng Guo4Duancheng Guo5Duancheng Guo6Department of Radiology, First People’s Hospital of Linping District, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Radiology, First People’s Hospital of Linping District, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaState Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, and School of Pharmacy, East China University of Science and Technology, Shanghai, ChinaCancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME), playing a pivotal role in tumor initiation, progression, and therapeutic resistance. This review explores the dual roles of CAFs in regulating tumor cell senescence and cell death, elucidating their mechanisms in inducing cellular senescence, shaping an immunosuppressive milieu, and modulating cell death pathways. CAFs promote tumor progression by secreting pro-inflammatory factors and extracellular matrix (ECM) components, while also contributing to metabolic reprogramming, immune evasion, and therapy resistance, thereby influencing anti-cancer treatment efficacy. Studies indicate that the heterogeneity and plasticity of CAFs determine their distinct functions across various tumor types. Consequently, precision-targeted therapeutic strategies against CAFs, including the elimination of senescent CAFs, inhibition of the senescence-associated secretory phenotype (SASP), and disruption of CAF-mediated cell death evasion mechanisms, have emerged as promising directions in cancer research. This review provides a comprehensive analysis of CAFs functions and their potential as therapeutic targets, offering valuable insights into the development of novel anti-cancer strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1635771/fullcancer-associated fibroblastscell senescencecell deathSASPTME |
| spellingShingle | Guixiang Ruan Xiang Wang Huiyi Ou Huiyi Ou Duancheng Guo Duancheng Guo Duancheng Guo Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapy Frontiers in Immunology cancer-associated fibroblasts cell senescence cell death SASP TME |
| title | Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapy |
| title_full | Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapy |
| title_fullStr | Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapy |
| title_full_unstemmed | Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapy |
| title_short | Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapy |
| title_sort | cancer associated fibroblasts dual roles from senescence sentinels to death regulators and new dimensions in therapy |
| topic | cancer-associated fibroblasts cell senescence cell death SASP TME |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1635771/full |
| work_keys_str_mv | AT guixiangruan cancerassociatedfibroblastsdualrolesfromsenescencesentinelstodeathregulatorsandnewdimensionsintherapy AT xiangwang cancerassociatedfibroblastsdualrolesfromsenescencesentinelstodeathregulatorsandnewdimensionsintherapy AT huiyiou cancerassociatedfibroblastsdualrolesfromsenescencesentinelstodeathregulatorsandnewdimensionsintherapy AT huiyiou cancerassociatedfibroblastsdualrolesfromsenescencesentinelstodeathregulatorsandnewdimensionsintherapy AT duanchengguo cancerassociatedfibroblastsdualrolesfromsenescencesentinelstodeathregulatorsandnewdimensionsintherapy AT duanchengguo cancerassociatedfibroblastsdualrolesfromsenescencesentinelstodeathregulatorsandnewdimensionsintherapy AT duanchengguo cancerassociatedfibroblastsdualrolesfromsenescencesentinelstodeathregulatorsandnewdimensionsintherapy |