Persistent accumulation of therapy-induced senescent cells: an obstacle to long-term cancer treatment efficacy.
10.1038/s41368-025-00380-w
- Author:
Jingjing LUO
1
;
Tongxu SUN
1
;
Zhenghui LIU
2
;
Yangfan LIU
1
;
Junjiang LIU
1
;
Shimeng WANG
1
;
Xueke SHI
3
;
Hongmei ZHOU
4
Author Information
1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & West China Hospital of Stomatology, Sichuan University, Chengdu, China.
2. Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
3. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & West China Hospital of Stomatology, Sichuan University, Chengdu, China. xueke.shi@scu.edu.cn.
4. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & West China Hospital of Stomatology, Sichuan University, Chengdu, China. zhouhm@scu.edu.cn.
- Publication Type:Review
- MeSH:
Humans;
Cellular Senescence/drug effects*;
Tumor Microenvironment;
Neoplasms/pathology*;
Senescence-Associated Secretory Phenotype
- From:
International Journal of Oral Science
2025;17(1):59-59
- CountryChina
- Language:English
-
Abstract:
In the ever-evolving landscape of cancer therapy, while cancer treatments such as chemotherapy, radiotherapy, and targeted therapy aim to eradicate malignant cells, they also inadvertently trigger cellular senescence in both cancerous and microenvironmental tissues. Therapy-induced senescence (TIS) can act as a barrier against tumor growth by halting cell proliferation in the short term, but the long-term persistence of therapy-induced senescent (TISnt) cells may pose a significant challenge in cancer management. Their distinct characteristics, like senescence-associated secretory phenotype (SASP), metabolic dysregulation, and immune evasion, make them exhibit remarkable heterogeneity to orchestrate the tumor microenvironment (TME), resulting in therapy resistance. However, how these TISnt cells functioning differently in cancer progression, and the intricate mechanisms by which they remodel the senescence-associated immunosuppressive microenvironment present challenges for improving anticancer therapy. Therefore, this review summarizes the heterogeneous TISnt cell phenotypes contributing to an accumulated senescent state, outlines their multidimensional interactions in the senescent microenvironment, and discusses current senescence-targeting strategies. Building on the current understanding of TIS, we propose potential avenues for improving TIS-targeting methodologies in the context of head and neck cancer, a representative heterogeneous malignancy, which can substantially enhance the efficacy of the "one-two punch" sequential treatment approach for head and neck cancer.
