Senolytics - charting a new course or enhancing existing anti-tumor therapies?

Sep 21, 2026

Cell senescence acts as an early anti-tumor barrier, yet the later accumulation of senescent cells can paradoxically drive cancer recurrence and harm surrounding tissues. This balance between proliferation and senescence is maintained partly through the senescence-associated secretory phenotype (SASP), which promotes chronic inflammation, tissue remodeling, and tumorigenesis via paracrine effects. Senotherapeutic senolytics selectively remove senescent cells, improving outcomes as monotherapies and in combination with chemo- or radiotherapy by clearing residual senescent cancer.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Abstract

Introduction

Rationale for senotherapy

Cellular senescence

Features of cellular senescence

Cellular Oncology (2025) 48:351–371 [https://doi.org/10.1007/s13402-024-01018-5](https://doi.org/10.1007/s13402-024-01018-5) REVIEW Senolytics: charting a new course or enhancing existing anti-tumor therapies? Konrad Czajkowski1 · Mariola Herbet1 · Marek Murias2 · Iwona Piątkowska-Chmiel1 Accepted: 21 November 2024 / Published online: 4 December 2024 © The Author(s) 2024 Abstract Cell senescence is a natural response within our organisms. Initially, it was considered an effective anti-tumor mechanism. However, it is now believed that while cell senescence initially acts as a robust barrier against tumor initiation, the subsequent accumulation of senescent cells can paradoxically promote cancer recurrence and cause damage to neighboring tissues. This intricate balance between cell proliferation and senescence plays a pivotal role in maintaining tissue homeostasis. Moreover, senescence cells secrete many bioactive molecules collectively termed the senescence-associated secretory phenotype (SASP), which can induce chronic inflammation, alter tissue architecture, and promote tumorigenesis through paracrine signaling. Among the myriads of compounds, senotherapeutic drugs have emerged as exceptionally promising candidates in anticancer treatment. Their ability to selectively target senescent cells while sparing healthy tissues represents a paradigm shift in therapeutic intervention, offering new avenues for personalized oncology medicine. Senolytics have introduced new therapeutic possibilities by enabling the targeted removal of senescent cells. As standalone agents, they can clear tumor cells in a senescent state and, when combined with chemo-or radiotherapy, eliminate residualsenescent cancer cells after treatment. This dual approach allows for the intentional use of lower-dose therapies or the removal of unintended senescent cells post-treatment. Additionally, by targeting non-cancerous senescent cells, senolytics may help reduce tumor formation risk, limit recurrence, and slow disease progression. This article examines the mechanisms of cellular senescence, its role in cancer treatment, and the importance of senotherapy, with particular attention to the therapeutic potential of senolytic drugs. 􀀍 Iwona Piątkowska-Chmiel [iwona.piatkowska-chmiel@umlub.pl](iwona.piatkowska-chmiel@umlub.pl) 1 Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Lublin, Poland 2 Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland Graphical abstract Keywords Cell senescence · Cancer · Senotherapy · SASP · One-Two Punch therapy 1 Introduction Cancer persists as one of the foremost health challenges in the contemporary world. In 2019, cancer was responsible for the deaths of over ten million people, making them the second leading cause of death after cardiovascular diseases [1]. The timely diagnosis of patients, coupled with intensive therapies that impose a considerable burden on the body [2], and the acceleration of aging in society [3], wherein the elderly demonstrate a heightened incidence of all cancer forms and the highest mortality rate [1], underscores the imperative for scientists to pursue novel, more efficacious, and less taxing therapies. Cellular senescence is a natural defense mechanism in our bodies [4] . Upon oncogenic activation, the body triggers cell senescence, inhibiting their proliferation, even at the pre-cancerous stage [4] . This mechanism is also evident in currently employed anticancer therapies [5] . Therapies like chemotherapy and radiotherapy, designed to induce extensive DNA damage and subsequently eliminate rapidly dividing cancer cells, have been found to provoke a robust senescence reaction [6] . Presently developed pro-senescence therapies concentrate on the deliberate induction of cellular senescence [7] . Research on these therapies points to a positive impact of senescence induction, particularly in the initial stages of the disease

FAQs

What is the dual role of cellular senescence in cancer?

Cell senescence initially suppresses tumor initiation by halting proliferation, but persistent senescent cells can later promote recurrence and damage nearby tissues.

How does the SASP contribute to tumor progression?

SASP drives chronic inflammation and alters tissue architecture, supporting tumorigenesis through paracrine signaling.

Why are senolytics considered promising anti-tumor therapies?

Senolytics target senescent cells while sparing healthy tissues, and they may enhance treatment by clearing residual senescent cancer cells after chemo- or radiotherapy.

Sep 21, 2026

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