Drug Enhances Cancer-killing Effect of Radiotherapy

Small drug molecule that releases hydrogen peroxide could boost the cancer-killing effect of radiation therapy, according to study led by scientists at University of Iowa, University of Texas Southwestern Medical Center, and Galera Therapeutics, Inc, who published their findings online in Science Translational Medicine. The study suggests that the drug's effect is based on a difference between the ability of cancer cells and healthy cells to withstand the damaging effects of hydrogen peroxide produced during the dismutation of superoxide.

Avasopasem manganese, made by Galera Therapeutics, acts like a natural enzyme called superoxide dismutase and converts superoxide into hydrogen peroxide.

The drug is currently in clinical trials to test its ability to protect mucosal tissue from the side-effect of radiotherapy.

Combining the drug with radiation therapy can generate high levels of hydrogen peroxide, which cannot harm normal tissue because healthy cells have metabolic systems that remove hydrogen peroxide. In contrast, cancer cells, which are biologically abnormal, can be overwhelmed by high levels of hydrogen peroxide.

"Cancer cells and healthy cells respond very differently to the increased amount of hydrogen peroxide," says Douglas Spitz, PhD, UI professor of radiation oncology and co-lead author of the study.

"Our study shows that Avasopasem manganese interacts synergistically with high doses of radiation to create hydrogen peroxide that selectively kill cancer cells but is relatively harmless to normal tissue."

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In mouse models of lung and pancreatic cancer the drug synergized with radiotherapy to such an extent that the treatment was able to destroy the tumors.

Greatest synergy occurred with high daily dose radiotherapy, similar to the doses delivered with Stereotactic Body Radiation Therapy (SBRT) currently used to treat some patients with cancer.

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"These findings are the result of collaborative efforts over several years by scientists primarily at Iowa, UT Southwestern Medical Center, and Galera, and are already being translated into several ongoing clinical studies," adds Spitz, who is a member of Holden Comprehensive Cancer Center at the UI.

"One of those early phase trials recently reported that Avasopasem manganese in combination with high daily dose radiotherapy appears to nearly double overall survival in patients with pancreatic cancer compared to a placebo plus the same radiotherapy.

Our study lays out the novel scientific basis for this potentially ground-breaking therapy for patients."



Source-Medindia