Cancer‑associated fibroblasts under therapy‑induced senescence in the tumor microenvironment (Review)

Zhang,Qiuhua; Lou,Yijie; Fang,Hao; Sun,Shaopeng; Jin,Rijuan; Ji,Yunxi; Chen,Zhe

doi:10.3892/etm.2024.12438

Cancer‑associated fibroblasts under therapy‑induced senescence in the tumor microenvironment (Review)

Authors:
- Qiuhua Zhang
- Yijie Lou
- Hao Fang
- Shaopeng Sun
- Rijuan Jin
- Yunxi Ji
- Zhe Chen
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Affiliations: Department of Oncology, First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of General Practice, First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang 310003, P.R. China, Key Laboratory of Digestive Pathophysiology of Zhejiang Province, Institute of Cancer Research, First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang 310003, P.R. China
Published online on: February 20, 2024 https://doi.org/10.3892/etm.2024.12438
Article Number: 150
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Current cancer treatments target tumor cells; however, the tumor microenvironment (TME) induces therapeutic resistance, tumor development and metastasis, thus rendering these treatments ineffective. Research on the TME has therefore concentrated on nonmalignant cells. Cancer‑associated fibroblasts (CAFs) are a major TME component, which contribute to cancer progression due to their diverse origins, phenotypes and functions, including cancer cell invasion and migration, extracellular matrix remodeling, tumor metabolism modulation and therapeutic resistance. Standard cancer treatment typically exacerbates the senescence‑associated secretory phenotype (SASP) of senescent cancer cells and nonmalignant cells that actively leak proinflammatory signals in the TME. Therapy‑induced senescence may impair cancer cell activity and compromise treatment responsiveness. CAFs and SASP are well‑studied in the formation and progression of cancer. The present review discusses the current data on CAF senescence caused by anticancer treatment and assesses how senescence‑like CAFs affect tumor formation. The development of senolytic medication for aging stromal cells is also highlighted. Combining cancer therapies with senolytics may boost therapeutic effects and provide novel possibilities for research.

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