Mechanisms underlying prostate cancer sensitivity to reactive oxygen species: overcoming radiotherapy resistance and recent clinical advances

Prostate cancer (PCa) is a leading cause of cancer-related mortality among men. Radiotherapy is the cornerstone of PCa treatment. However, a major limitation of radiotherapy is the development of resistance, which compromises treatment efficacy. Reactive oxygen species (ROS), which are generated by...

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Main Authors: Meidan Wang, Rui Xing, Liqun Wang, Mingyue Pan, Ruoyun Zhang, Ting Li, Weiqiang Sun, Jing Zhou
Format: Article
Language:English
Published: China Anti-Cancer Association 2025-07-01
Series:Cancer Biology & Medicine
Subjects:
Online Access:https://www.cancerbiomed.org/content/22/7/747
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author Meidan Wang
Rui Xing
Liqun Wang
Mingyue Pan
Ruoyun Zhang
Ting Li
Weiqiang Sun
Jing Zhou
author_facet Meidan Wang
Rui Xing
Liqun Wang
Mingyue Pan
Ruoyun Zhang
Ting Li
Weiqiang Sun
Jing Zhou
author_sort Meidan Wang
collection DOAJ
description Prostate cancer (PCa) is a leading cause of cancer-related mortality among men. Radiotherapy is the cornerstone of PCa treatment. However, a major limitation of radiotherapy is the development of resistance, which compromises treatment efficacy. Reactive oxygen species (ROS), which are generated by radiation, have a dual role in PCa by inducing DNA damage and apoptosis, while also promoting tumor progression and radioresistance. Elevated ROS levels enhance metabolic reprogramming, activate oncogenic pathways, and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition (EMT). Key molecular mechanisms, including the Nrf2/Keap1 signaling axis, Bcl-2 mutations, and Speckle-type POZ protein alterations, contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity. Additionally, the interplay between hypoxia, androgen receptor variants (AR-Vs), and ferroptosis regulators further influence radiotherapy outcomes. Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.
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institution Kabale University
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publisher China Anti-Cancer Association
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series Cancer Biology & Medicine
spelling doaj-art-fa4418c1e7964be4bb7372b63b4d27772025-08-20T03:35:12ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412025-07-0122774776110.20892/j.issn.2095-3941.2024.0584Mechanisms underlying prostate cancer sensitivity to reactive oxygen species: overcoming radiotherapy resistance and recent clinical advancesMeidan Wang0Rui Xing1Liqun Wang2Mingyue Pan3Ruoyun Zhang4Ting Li5Weiqiang Sun6Jing Zhou7Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg 79106, GermanyDepartment of Hematology, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang People’s Hospital, Dongyang 322100, ChinaDepartment of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg 79106, GermanyFaculty of Law, University of Freiburg, Freiburg 79085, GermanySchool of Chinese Language and Literature, Tangshan Normal University, Tangshan 063000, ChinaDepartment of Oncology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaDepartment of Hepatobiliary Surgery, General Surgery, Jinan Third People’s Hospital, Jinan 250031, ChinaDepartment of Chemoradiotherapy, Ningbo NO. 2 Hospital, Ningbo 315010, ChinaProstate cancer (PCa) is a leading cause of cancer-related mortality among men. Radiotherapy is the cornerstone of PCa treatment. However, a major limitation of radiotherapy is the development of resistance, which compromises treatment efficacy. Reactive oxygen species (ROS), which are generated by radiation, have a dual role in PCa by inducing DNA damage and apoptosis, while also promoting tumor progression and radioresistance. Elevated ROS levels enhance metabolic reprogramming, activate oncogenic pathways, and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition (EMT). Key molecular mechanisms, including the Nrf2/Keap1 signaling axis, Bcl-2 mutations, and Speckle-type POZ protein alterations, contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity. Additionally, the interplay between hypoxia, androgen receptor variants (AR-Vs), and ferroptosis regulators further influence radiotherapy outcomes. Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.https://www.cancerbiomed.org/content/22/7/747prostate cancer (pca)radiation therapy (rt)reactive oxygen species (ros)radiotherapy resistanceantioxidants
spellingShingle Meidan Wang
Rui Xing
Liqun Wang
Mingyue Pan
Ruoyun Zhang
Ting Li
Weiqiang Sun
Jing Zhou
Mechanisms underlying prostate cancer sensitivity to reactive oxygen species: overcoming radiotherapy resistance and recent clinical advances
Cancer Biology & Medicine
prostate cancer (pca)
radiation therapy (rt)
reactive oxygen species (ros)
radiotherapy resistance
antioxidants
title Mechanisms underlying prostate cancer sensitivity to reactive oxygen species: overcoming radiotherapy resistance and recent clinical advances
title_full Mechanisms underlying prostate cancer sensitivity to reactive oxygen species: overcoming radiotherapy resistance and recent clinical advances
title_fullStr Mechanisms underlying prostate cancer sensitivity to reactive oxygen species: overcoming radiotherapy resistance and recent clinical advances
title_full_unstemmed Mechanisms underlying prostate cancer sensitivity to reactive oxygen species: overcoming radiotherapy resistance and recent clinical advances
title_short Mechanisms underlying prostate cancer sensitivity to reactive oxygen species: overcoming radiotherapy resistance and recent clinical advances
title_sort mechanisms underlying prostate cancer sensitivity to reactive oxygen species overcoming radiotherapy resistance and recent clinical advances
topic prostate cancer (pca)
radiation therapy (rt)
reactive oxygen species (ros)
radiotherapy resistance
antioxidants
url https://www.cancerbiomed.org/content/22/7/747
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