Cancer chemotherapy and pharmacology
Pharmacological targeting of xCT/system Xc- to modulate temozolomide sensitivity in glioma and glioblastoma preclinical models: a focused systematic review
By Elhashani S, Elkawafi M, El Shekhi A and 2 others.
Abstract
Background
Resistance to temozolomide (TMZ) remains a major barrier in glioblastoma treatment. The cystine/glutamate antiporter system Xc-, mainly through its xCT/SLC7A11 light-chain subunit, supports cystine uptake, glutathione synthesis and redox balance, making it a biologically plausible target for modifying TMZ response. This focused systematic review evaluated whether pharmacological xCT/system Xc--relevant inhibition enhances TMZ sensitivity in glioma/glioblastoma preclinical models.
Methods
Searches were conducted in Web of Science, PubMed/MEDLINE and the Cochrane Library, with supplementary Google Scholar screening, and were completed on 30 April 2026. Reference lists of the included preclinical studies were also screened as a supplementary citation-chasing method. No lower publication-date restriction was applied. Eligible studies were primary preclinical studies using glioma/glioblastoma models, TMZ treatment, and TMZ combined with a pharmacological xCT/system Xc--relevant inhibitor or related intervention. Because the included studies differed in models, inhibitors, formulations, treatment conditions and outcome measures, findings were synthesised narratively.