JUN 30, 2020 6:21 AM PDT

PAR glycohydrolase inhibitors to enhance treatment for gliomas

New hope for glioma patients comes in the form of a novel strategy to target tumors, the results of which are published in Cancer Discovery, a journal of the American Association for Cancer Research. The research was spearheaded by investigators at Massachusetts General Hospital who hope to inform mechanisms that will improve treatment options for the disease. 

While patients with glioma brain tumors can receive surgery, radiation, and chemotherapy, these treatment options do not always offer a cure to the disease. However, past work led by Mass General's Daniel Cahill, MD, Ph.D., Hiroaki Wakimoto, MD, Ph.D., and Julie Miller, MD, Ph.D., demonstrated how mutations in the isocitrate dehydrogenase (IDH) genes have a metabolic Achilles heel. What they found is that mutant IDH genes are particularly susceptible to treatments that lower levels of NAD+, an important metabolic molecule. 

So the researchers combined this knowledge with another key piece of information: chemotherapy activates an enzyme that stimulates NAD+ molecules to unite to produce poly(ADP-ribose), or PAR, which is a key DNA damage signal. And it only does this in IDH mutant glioma cells, not healthy cells. 

Knowing this, the researchers figured this provided the perfect opportunity to target IDH mutant glioma cells by maintaining high PAR levels and low NAD+ levels through chemotherapy.

Gliomas account for about 25% of childhood cancers. Photo: Pixabay

"We found that maximum effectiveness was achieved by combining two agents: temozolomide, the chemotherapy most commonly used to treat patients with IDH mutant gliomas, with a drug that blocks PAR breakdown, known as a PAR glycohydrolase inhibitor," said Dr. Cahill, 

Dr. Wakimoto continues, explaining: "We showed, for the first time, that PAR glycohydrolase inhibitors can be used to enhance the effectiveness of chemotherapy in tumors with metabolic weaknesses in the NAD+ pathway.”

Dr. Miller concludes that their findings have real-life implications for glioma patients. "The long-term significance is that, based on our findings, they could be tested in individuals with IDH mutant gliomas, with a goal of hopefully improving outcomes in these patients," she said.

Sources: Cancer Discovery, Eureka Alert

About the Author
  • Kathryn is a curious world-traveller interested in the intersection between nature, culture, history, and people. She has worked for environmental education non-profits and is a Spanish/English interpreter.
You May Also Like
AUG 05, 2020
Cancer
A New Test to Analyze Cell-Free DNA in Cancer Diagnostics
AUG 05, 2020
A New Test to Analyze Cell-Free DNA in Cancer Diagnostics
Cell-free DNA (cfDNA) are small pieces of genomic DNA that have escaped into the bloodstream either through active relea ...
SEP 17, 2020
Cardiology
Can Grape Polyphenol Extracts prevent Cardiotoxicity?
SEP 17, 2020
Can Grape Polyphenol Extracts prevent Cardiotoxicity?
One of the biggest issues with chemotherapy treatments is their inherent toxicities. Most chemotherapy drugs are toxic t ...
SEP 23, 2020
Cancer
Can Increased Pain Indicate Oral Cancer?
SEP 23, 2020
Can Increased Pain Indicate Oral Cancer?
The human body has many ways of letting you know something is wrong. It can send signals to tell you that you are hungry ...
OCT 07, 2020
Cancer
Beyond the eye: improving melanoma detection
OCT 07, 2020
Beyond the eye: improving melanoma detection
Research from UC San Francisco reports that it is possible to use genomic methods to detect skin damage from the sun not ...
OCT 14, 2020
Cancer
Using Plasma Scalpels with Chemotherapy Against Brain Cancer
OCT 14, 2020
Using Plasma Scalpels with Chemotherapy Against Brain Cancer
Cold atmospheric plasma is a relatively new technique that utilizes a tool that generates a sort of plasma scalpel, exce ...
OCT 12, 2020
Drug Discovery & Development
Researchers Solve Key Problem for Cancer Immunotherapy
OCT 12, 2020
Researchers Solve Key Problem for Cancer Immunotherapy
Cancer immunotherapies are becoming increasingly promising as a standard-of-care treatment. However, despite their promi ...
Loading Comments...