Cellular senescence in cancer: Barrier, driver, and therapeutic opportunity

Yuan Huozhong; Ding Qianzhe; Zhao Limin

doi:10.70401/acrt.2026.0046

Cellular senescence in cancer: Barrier, driver, and therapeutic opportunity

Huozhong Yuan

1,#

Qianzhe Ding

2,#

Limin Zhao

2,*

Affiliation +

*Correspondence to: Limin Zhao, Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Human Aging, Nanchang 330031, Jiangxi, China. E-mail: zhaolimin@ncu.edu.cn

Ageing Cancer Res Treat. 2027;4:202635. 10.70401/acrt.2026.0046

Received: August 11, 2026Accepted: November 10, 2026Published: November 11, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Cellular senescence plays a context-dependent dual role in tumor progression. Transitioning from a tumor-suppressive barrier in premalignant stages to a tumor-promoting driver during progression, and further to double-edged effects in therapy, its functional shift involves complex molecular mechanisms and microenvironmental interactions. This review outlines the relationship between aging and cancer; describes the characteristics, functions, and clinical potential of cellular senescence in cancer; and the transition from tumor suppression to tumor promotion. Specifically, we examine how this transition is driven by immune clearance failure, NOTCH1-regulated SASP shifts, the positive feedback loop between senescence accumulation and immunosuppression, and mesenchymal drift. We also discuss the possibility that senescent cells act as a reservoir for malignant transformation, and that tumor cells escaping clearance may retain a “reversible senescence memory.” Finally, we highlight current therapeutic strategies targeting senescence, including senolytics and senomorphics, and critically assess the risks of improper senolytic use. Together, these insights offer new perspectives on the central role of senescence in tumorigenesis and progression.

Keywords

Cellular senescence, aging, cancer, therapeutic strategies, reversible senescence memory

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Yuan H, Ding Q, Zhao L. Cellular senescence in cancer: Barrier, driver, and therapeutic opportunity. Ageing Cancer Res Treat. 2027;4:202635. https://doi.org/10.70401/acrt.2026.0046