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Publications

Journal Article Review Ahead of print 6 citations

PubMed: 40992550 DOI: 10.1016/j.gene.2025.149774

Therapy-induced senescence in prostate cancer: Mechanisms, therapeutic strategies, and clinical implications.

Gene

Authors: Luisa Bacca, Julian Brandariz, Francesca Zacchi, Andrea Zivi, Joaquin Mateo, David P Labbé

Affiliations

  • Cancer Research Program, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada; Division of Clinical and Translational Research, Department of Medicine, McGill University, Montréal, Québec, Canada.
  • Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
  • Section of Innovation Biomedicine-Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona and University and Hospital Trust (AOUI) of Verona, Verona, Italy.
  • Section of Innovation Biomedicine-Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona and University and Hospital Trust (AOUI) of Verona, Verona, Italy.
  • Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Medical Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
  • Cancer Research Program, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada; Division of Clinical and Translational Research, Department of Medicine, McGill University, Montréal, Québec, Canada; Division of Urology, Department of Surgery, McGill University, Montréal, Québec, Canada.

Abstract

Prostate cancer (PCa) remains a major cause of cancer-related mortality in men, particularly in its advanced and metastatic stages. While various systemic therapies have improved clinical outcomes, therapy resistance and disease progression remain significant challenges. One critical, yet underappreciated, mechanism influencing treatment response is therapy-induced senescence (TIS), a stable form of cell cycle arrest triggered by anticancer treatments. In PCa, TIS can be elicited by chemotherapy, radiotherapy, hormonal therapies, and targeted agents, and is characterized by a complex interplay of tumor-suppressive and tumor-promoting effects, largely mediated through the senescence-associated secretory phenotype (SASP). This review explores the molecular mechanisms of senescence, the diverse therapeutic strategies that induce it, and the dual roles it plays in PCa progression and treatment resistance. We further discuss emerging approaches that combine senescence-inducing therapies with senescence-targeting strategies, such as senolytics and senomorphics, to mitigate the adverse consequences of persistent senescent PCa cells. Finally, we highlight ongoing clinical trials, translational barriers, and future directions in integrating senotherapy into the clinical management of PCa.

MeSH

Cells, Recombination, Genetic, Molecular Biology, Neoplasms, Prostate, Prostatic Neoplasms, Therapeutics