A study by the University of Michigan identifies why people with glioma, a type of tumor, tend to live much longer than others.
The research was funded by the National Institutes of Health, which suggested that the combination of radiation therapy against cancer to block DNA repair could be an effective treatment.
Some patients are less aggressive and can repair DNA better than others, but they are difficult to eliminate by radiation. The research article was published on February 13, 2019 in the journal Science Translation Magazine.
Researchers have focused on low-grade gliomas. These gliomas are carriers of a disease that causes changes in a gene called isocitrate dehydrogenase 1 (IDH1). These changes are found in about 50% of cases with low levels of primary glioma.
Findings
According to the research, patients with glioma have changes in IDH1 are mostly of young age. In addition, they live longer than patients with normal genes.
The experiment was performed by replicating the patient’s tumor by genetic programming of mice to increase cancer cells in the brain. These cells carry pathogenic mutations in IDH1 as well as mutations in TP53 (a tumor suppressor gene) and ATRX (a DNA-protein complex remodeling gene).
In terms of patients, the results of the study showed that mice programmed to develop brain cells tend to live longer than control mice when the tumors were programmed for normal IDH1.
The study also showed that the IDH1 mutation had made the glioma cells less aggressive. When implanted in the brain of mice, it was very likely that cell division increased tumor growth at lower rates.
IDH1 mutations as well as mutations of the TP53 and ATRX genes lead to the resistance of the tumor to ionizing radiation. This treatment often damages the DNA by killing the cells.
Subsequent studies have shown that IDH1 alters activity due to a pathogenic mutation. For this reason, several chemical reactions that alter the genes of the cancerous cells begin in a way that increases the production of a protein that can repair the damaged DNA.
Dr. Maria G. Castro, professor of neurosurgery at Michigan Medicine and principal author of the study, said,
“Our team’s mission is to find life-saving treatments for these patients. The results from this study could be a blueprint for extending, if not saving, the lives of many patients.”
Dr. Jane Fountain, a presenter at the National Institute of Neurological Diseases and Stroke at NIH, said:
“These findings have the potential to impact many younger glioma patients with low-grade tumors by either ‘curing’ them or extending their lives, the preclinical model Dr. Castro’s team developed will be extremely valuable to cancer researchers. It closely mirrors the human disease.”
In this study, researchers formulated and experimented with a new combination therapy. They found that mice exposed to mutated IDH1 tumors with radiation and injected with cancer drugs to prevent DNA repair can prolong life.
In contrast, mice showed no side effects when treated or radiated individually. Similar results were observed in human gliomas grown in a Petri dish.