The drug, acetazolamide, was investigated
in a study published this month in Science Translational
Medicine, which found that it helped to overcome resistance to
chemotherapy drug temozolomide (TMZ). TMZ is frequently used in the treatment
of gliomas, but some patients do not respond to the treatment. With the
addition of acetazolamide, researchers identified an improvement in survival in
pre-clinical models of glioma.
TMZ acts by damaging the DNA inside tumour
cells, causing them to die. However, some tumour cells can block or repair this
DNA damage, which limits the impact of chemotherapy. The study identified that
the patients who were unresponsive to TMZ had high levels of a protein BCL-3.
Researchers determined that this protein was responsible for shielding cancer
cells from TMZ damage, by activating a protective enzyme called carbonic
Acetazolamide is a carbonic anhydrase inhibitor. This makes the drug able to restore the ability of TMZ to kill tumour cells. The drug, sold under the trade name Diamox, is “cheap to make, easy to take and has limited side effects”, according to study
director Professor Bahktiar Yamini from the University of Chicago.
When taken in combination with TMZ, the drug resulted in a 30 to 40 per cent
increase in survival in animal models.
"An important feature of predictors like BCL-3 is that they are informative," the authors note. "They can identify pathways to improve treatment response." By examining those pathways, the authors identified carbonic anhydrase inhibitors, such as acetazolamide, to reduce resistance to TMZ.
This research is being fed into a phase
1 clinical trial, to examine the efficacy and safety of
acetazolamide in combination with TMZ in humans. The trial will investigate the
drug combination in patients with malignant astrocytoma, which will soon begin enrolling
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