Bioelectromagnetic fields in prostate cancer: molecular mechanisms and therapeutic implications

Prostate cancer (PCa) remains a global health challenge, with emerging evidence implicating environmental electromagnetic fields (EMFs) as dual regulators of tumor progression and therapeutic innovation. This perspective synthesizes mechanistic insights into EMFs bioeffects through three interconnected axes: (1) Calcium signaling as a central biosensor, translating EMFs stimuli into oncogenic processes via piezoelectric and ionic mechanisms; (2) Extracellular vesicles (EVs)-mediated metastatic reprogramming through cargo remodeling (e.g., pro-inflammatory proteins) and dysregulation of oncogenic miRNAs; and (3) Ferroptosis, a frequency-modulated cell death pathway driven by calcium-iron-reactive oxygen species (ROS) crosstalk. Paradoxically, EMFs exhibit context-dependent duality: low-intensity fields exacerbate malignancy by rewiring calcium/EVs-driven tumor-microenvironment interactions, while high-intensity fields achieve tumor ablation via calcium overload, ferroptosis, hyperthermia, or electroporation. Novel strategies, such as PEGylated nanocrystals combined with intratumoral micromagnets, synergize ferroptosis with immunogenic cell death, demonstrating therapeutic potential with minimal toxicity. Our analysis underscores the critical need for parameter optimization (frequency, intensity, duration) to balance oncogenic risks against therapeutic precision. We propose that integrating biophysical targeting with electromagnetic engineering holds promise to redefine PCa management through mechanism-driven precision. This perspective aims to frame these insights and highlight their implications for future research and therapeutic development.