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Study Finds Acetazolamide May Be Effective in Treating Glioblastoma

Alison Rodriguez
Acetazolamide, sold under the trade name Diamox, is a drug used to treat altitude sickness, glaucoma, epilepsy, heart failure, and seizures. According to a new study, acetazolamide may also be effective in treating the fast-growing brain tumor glioblastoma.
Acetazolamide, sold under the trade name Diamox, is a drug used to treat altitude sickness, glaucoma, epilepsy, heart failure, and seizures. According to a new study, acetazolamide may also be effective in treating the fast-growing brain tumor glioblastoma.

The drug temozolomide (TMZ) is the most frequently used chemotherapy for treating gliomas; however, not all patients respond to treatment with this drug. TMZ damages DNA in a way that can kill tumor cells, but some tumor cells can block or repair the DNA damage, according to a report.

“Although alkylators like temozolomide (TMZ) improve overall patient survival, many patients experience minimal benefit from their use. These observations underline the critical need for predictors of response to alkylating therapy,” the study explained.

The study found that most patients with glioma who had high levels of the protein BCL-3 (B cell CLL/lymphoma 3) were unresponsive to TMZ because BCL-3 shields cancer cells from the TMZ damage by activating the protective enzyme called carbonic anhydrase II, according to the study.

Although acetazolamide is a carbonic anhydrase inhibitor, it can restore TMZ’s ability to kill the tumor cells. During the study, the researchers added acetazolamide to TMZ , which enabled mice with gliomas to survive longer. Additionally, when this combination treatment was used in several animal models, it resulted in a 30% to 40% increase in survival time, noted the study director Bahktiar Yamini, MD, a neurosurgery professor at the University of Chicago Medicine.

“This finding, when considered with the observation that BCL-3 is a candidate oncoprotein that has never been identified as a glioma driver, indicates that BCL3 loss is a passenger event unrelated to glioma formation,” the researchers stated. “Although the ability of passenger events to promote unintended therapeutic susceptibility has been shown in animal models, the link between loss of BCL-3 and TMZ susceptibility demonstrates the importance of passenger modification to chemosensitivity in a clinical setting.”

Furthermore, when the researchers looked back at previous human studies, they discovered that patients with lower levels of BCL-3 who were treated with TMZ had, overall, survived longer than those who had high levels of the biomarker.

The authors emphasized that, in the future, a prospective randomized clinical trial is necessary in order to validate that the use of BCL-3 to predict which patients will benefit from TMZ. They also suggested that the combination of acetazolamide with TMZ may be an effective subgroup to consider for the trial for patients with high BCL-3 expression.

 
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