Targeting senescence as an anticancer therapy

Cellular senescence is a stress response elicited by different molecular insults. Senescence results in cell cycle exit and is characterised by multiple phenotypic changes such as the production of a bioactive secretome. Senescent cells accumulate during ageing and are present in cancerous and fibro...

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Bibliographic Details
Main Authors: Laura Bousset, Jesús Gil
Format: Article
Language:English
Published: Wiley 2022-11-01
Series:Molecular Oncology
Subjects:
Online Access:https://doi.org/10.1002/1878-0261.13312
Description
Summary:Cellular senescence is a stress response elicited by different molecular insults. Senescence results in cell cycle exit and is characterised by multiple phenotypic changes such as the production of a bioactive secretome. Senescent cells accumulate during ageing and are present in cancerous and fibrotic lesions. Drugs that selectively kill senescent cells (senolytics) have shown great promise for the treatment of age‐related diseases. Senescence plays paradoxical roles in cancer. Induction of senescence limits cancer progression and contributes to therapy success, but lingering senescent cells fuel progression, recurrence, and metastasis. In this review, we describe the intricate relation between senescence and cancer. Moreover, we enumerate how current anticancer therapies induce senescence in tumour cells and how senolytic agents could be deployed to complement anticancer therapies. “One‐two punch” therapies aim to first induce senescence in the tumour followed by senolytic treatment to target newly exposed vulnerabilities in senescent tumour cells. “One‐two punch” represents an emerging and promising new strategy in cancer treatment. Future challenges of “one‐two punch” approaches include how to best monitor senescence in cancer patients to effectively survey their efficacy.
ISSN:1574-7891
1878-0261