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Acetazolamide + temozolomide is an investigational combination therapy being studied primarily for the treatment of glioblastoma and other high-grade gliomas. Acetazolamide is a carbonic anhydrase inhibitor traditionally used to treat conditions such as glaucoma, epilepsy, altitude sickness, and edema. Temozolomide is an oral alkylating agent widely used in the standard care of malignant gliomas, particularly glioblastoma multiforme. Preclinical studies have shown that acetazolamide can sensitize tumor cells to temozolomide by inhibiting BCL-3-dependent upregulation of carbonic anhydrase II, which otherwise confers resistance to temozolomide. The combination aims to overcome this resistance mechanism and improve therapeutic outcomes in patients with MGMT promoter-methylated IDH wildtype glioblastoma[4][5][8]. Early phase I clinical trials indicate that this combination is safe and tolerable when administered during the adjuvant phase of standard temozolomide therapy[2][4].
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