Altitude sickness drug appears to slow progression of glioblastoma

July 9, 2018, University of Chicago Medical Center
Bahktiar Yamini, MD, a professor of neurosurgery at the University of Chicago Medicine Credit: The University of Chicago Medicine

A drug used to treat altitude sickness—as well as glaucoma, epilepsy, heart failure and seizures—may also offer significant gains for patients with a fast-growing brain tumor known as glioblastoma, according to a study published July 4, 2018, in the journal Science Translational Medicine.

The drug, acetazolamide, sold under the trade name Diamox, is "cheap to make, easy to take and has limited side effects," said study director Bahktiar Yamini, MD, a professor of neurosurgery at the University of Chicago Medicine.

"I take it myself, whenever I go to the Rocky Mountains," he said, "two pills a day." The most common side effect of Diamox is "a metallic taste when drinking something carbonated."

The most frequently used chemotherapy for gliomas is a drug called temozolomide (TMZ). However, not all patients respond to this drug. Median survival with this disease is about 14 months.

TMZ acts by damaging DNA in ways that can kill tumor cells. But some tumor cells are able to block or repair this type of DNA damage. This limits the drug's impact.

The researchers found that most glioma patients with high levels of a protein called BCL-3 (B cell CLL/lymphoma 3) were unresponsive to the beneficial effects of TMZ. BCL-3 shields cancer cells from TMZ damage by activating a protective enzyme known as carbonic anhydrase II.

Acetazolamide, however, is a carbonic anhydrase inhibitor. It can restore TMZ's ability to kill . Adding acetazolamide to TMZ enabled mice with gliomas to survive longer.

"We tested this combination treatment strategy in several animal models," Yamini said. It cured some of them. Others had a 30 to 40 percent increase in survival time.

When Yamini and colleagues looked at BCL-3 level from previous human studies, they found that patients with lower levels of BCL-3 who were treated with TMZ survived longer than patients who had high levels of this biomarker.

"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 inhibitors, such as acetazolamide, as a way to reduce resistance to temozolomide.

"Our data," they note, demonstrate that it is the "induction of CAII by TMZ that is important in modulating response to therapy."

Validating the use of BCL-3 to predict which patients will benefit from the use of temozolomide will require verification in a prospective , the authors note. They also suggest that repurposing along with temozolamide might be particularly effective in a subgroup of appropriate patients with tumors that have high BCL-3 expression. They have already organized a trial at several Chicago area institutions and hope to recruit soon.

Explore further: Enzyme inhibitor combined with chemotherapy delays glioblastoma growth

More information: Longtao Wu et al, BCL3 expression promotes resistance to alkylating chemotherapy in gliomas, Science Translational Medicine (2018). DOI: 10.1126/scitranslmed.aar2238

Related Stories

Enzyme inhibitor combined with chemotherapy delays glioblastoma growth

January 23, 2018
In animal experiments, a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and the standard glioblastoma chemotherapy drug, temozolomide.

Genetic biomarker linked to improved survival for patients with certain brain tumors

June 28, 2018
A DNA-level biomarker (MGMT promoter methylation) can be used to help predict survival outcomes in patients with high-risk, low-grade gliomas, according to a new study conducted through the NRG Oncology/RTOG collaborative ...

Researchers find leukemia and lymphoma drug may benefit glioblastoma patients

May 30, 2018
New Cleveland Clinic research shows for the first time that ibrutinib, an FDA-approved drug for lymphoma and leukemia, may also help treat the most common—and deadliest—type of brain tumor. The findings, published in ...

Combination chemotherapy may significantly improve treatment for deadly brain tumor

January 22, 2018
A diagnosis of the brain cancer glioblastoma carries a dismal prognosis, with most patients dying within five years. Now a team led by Massachusetts General Hospital (MGH) investigators has found that adding the chemotherapy ...

Enzyme blocker stops growth of deadly brain tumor

May 11, 2018
Investigators were able to halt the growth of glioblastoma, an aggressive form of brain cancer, by inhibiting an enzyme called CDK5, according to a Northwestern Medicine study published in Cell Reports.

Recommended for you

Photoacoustic imaging may help doctors detect ovarian tumors earlier

November 14, 2018
Ovarian cancer claims the lives of more than 14,000 in the U.S. each year, ranking fifth among cancer deaths in women. A multidisciplinary team at Washington University in St. Louis has found an innovative way to use sound ...

New antibody breakthrough to lead the fight against cancer

November 14, 2018
Scientists at the University of Southampton have developed a new antibody that could hold the key to unlocking cancer's defence against the body's immune system.

Solving the mystery of NPM1 in acute myeloid leukemia

November 13, 2018
Although it has long been recognized that mutations of gene NPM1 play an important role in acute myeloid leukemia, no one has determined how the normal and the mutated forms of the protein NPM1 function.

Cognitive decline—radiation—brain tumor prevented by temporarily shutting down immune response

November 13, 2018
Treating brain tumors comes at a steep cost, especially for children. More than half of patients who endure radiation therapy for these tumors experience irreversible cognitive decline, a side-effect that has particularly ...

Study finds promising therapeutic target for aggressive type of breast cancer

November 13, 2018
A new Nature Communications study led by University of Kentucky Markey Cancer Center researchers suggests that an enzyme known as Prolyl 4-hydroxylase subunit alpha-1 (P4HA1) is a potential therapeutic target for triple negative ...

Scientists shine new light on link between obesity and cancer

November 12, 2018
Scientists have made a major discovery that shines a new, explanatory light on the link between obesity and cancer. Their research confirms why the body's immune surveillance systems—led by cancer-fighting Natural Killer ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.