sulfasalazine + temozolomide

This is a combination of two small molecule drugs, sulfasalazine and temozolomide. Sulfasalazine is an anti-inflammatory agent primarily used for inflammatory bowel disease and rheumatoid arthritis, with additional mechanisms including inhibition of the glutamate-cystine antiporter (system Xc-) and nuclear factor kappa B (NFκB), as well as induction of ferroptosis in cancer cells. Temozolomide is an oral alkylating agent used mainly in the treatment of glioblastoma multiforme and other high-grade gliomas; it acts by methylating DNA at the O6 and N7 positions of guanine, leading to DNA damage and cell death. The combination has been investigated for synergistic cytotoxic effects against glioblastoma cells, where sulfasalazine enhances temozolomide's efficacy by depleting glutathione levels through system Xc- inhibition, thereby increasing oxidative stress in tumor cells. Clinical studies have explored this combination with radiotherapy for newly diagnosed glioblastoma but reported high rates of hematologic toxicity leading to discontinuation[1][2][4].