This review addresses the challenge of radioresistance in cervical cancer by exploring the role of ferroptosis in enhancing the efficacy of radiotherapy (RT). It emphasizes the radiosensitizing effect of β-sitosterol through modulation of the GPX4/ACSL4 axis. β-Sitosterol targets mitochondrial membranes, inhibits GPX4 activity, and activates ACSL4, promoting polyunsaturated fatty acid synthesis and thereby facilitating ferroptosis. Preclinical models demonstrate that β-sitosterol significantly improves RT sensitivity and increases tumor iron accumulation. The review further proposes a predictive framework based on ox-LDL levels and the ACSL4/GPX4 ratio for potential clinical application, alongside discussions on innovative delivery systems, ferroptosis-apoptosis interactions, microbiota-mediated metabolic effects, and AI-driven optimization of RT-- drug combinations. These insights contribute to advancing personalized radiotherapy strategies for cervical cancer.
Xiao et al. (Mon,) studied this question.