Dietary modulation of ferroptosis sensitivity in glioblastoma and other treatment-resistant cancers

Olivia E. Gilbert

Sebastian John

Ali D. Fahim

Dominique M.O. Higgins

*Correspondence to: Olivia E. Gilbert, Department of Neurosurgery, University of North Carolina, Chapel Hill, NC 27599, USA. E-mail: olivia.gilbert@unchealth.unc.edu

Ferroptosis Oxid Stress. 2027;3:202631. 10.70401/fos.2026.0042

Received: July 01, 2026Accepted: August 31, 2026Published: August 31, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Ferroptosis sensitivity in cancer cells is directly governed by cellular metabolism and nutritional inputs, including amino acid availability, lipid composition, and redox homeostasis. This suggests that dietary interventions might systemically shift the metabolic landscape of tumors toward ferroptotic susceptibility. Specifically, dietary restriction of methionine and cysteine, iron supplementation, selenium or lipid modulation, ketogenic diets, and fasting-mimicking regimens each target distinct aspects of the ferroptosis regulatory network and offer pharmacologic parallels that converge on complementary mechanisms. In GBM, preclinical studies demonstrate that restriction of dietary methionine and cysteine sensitizes gliomas to ferroptosis and synergizes with GPX4 inhibitors, while radiation itself triggers ferroptotic cell death. Emerging data extend these principles across multiple tumor types, including pancreatic, gastric, esophageal, and colorectal cancers, as well as leukemia, suggesting broad applicability. Here, we synthesize the rapidly growing literature that links these nutritional interventions to ferroptosis sensitization in cancer, with particular focus on GBM as a paradigmatic treatment-resistant malignancy.

Keywords

Dietary, ketogenic, glioblastoma, lipid, amino acid, methionine, cysteine, cysteine and methionine deprivation, ferroptosis, iron, selenium

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Gilbert OE, John S, Fahim AD, Higgins DM. Dietary modulation of ferroptosis sensitivity in glioblastoma and other treatment-resistant cancers. Ferroptosis Oxid Stress. 2027;3:202631. https://doi.org/10.70401/fos.2026.0042