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

作者：Meidan Wang, Rui Xing, Liqun Wang, Mingyue Pan, Ruoyun Zhang, Ting Li, Wei Sun, Jing Zhou · 发表于：Cancer Biology and Medicine · 年份：2025 · DOI：10.20892/j.issn.2095-3941.2024.0584 · 被引用次数：3 · 研究领域：Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research、Cancer, Lipids, and Metabolism

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.