A study conducted by the University of Michigan finds out the reason why people with gliomas, a type of tumor, tend to live remarkably longer than others.
The National Institutes of Health funded the research which suggested that combining radiation therapy with cancer drugs in order to block DNA repair might prove to be an effective treatment.
The outcomes proposed that tumor cells of certain patients are less aggressive and better at fixing DNA than others however are hard to eliminate with radiation. The research paper was published in Science Translation Magazine on 13 Feb 2019.
The researchers emphasized on low-grade gliomas. These gliomas carry an illness which causes changes in a gene called isocitrate dehydrogenase 1 (IDH1). These changes are found in about 50 percent of cases of primary low-grade gliomas.
Findings of the research
According to the research, patients suffering from glioma, whose tumors have changes in IDH1 are mostly of young age. Also, they live longer than those patients who have a normal gene.
The experiment was done by recreating the patient’s tumor by genetically programming mice to grow brain cancer cells. These cells carry disease-causing mutations in IDH1 along with mutations in TP53 ( a tumor suppressor gene) and ATRX ( a DNA-protein complex remodeling gene).
Similar to the patients, the results of the study showed that the mice which were programmed to grow brain cells tend to live longer in comparison to the control mice whose tumors were programmed to have normal IDH1.
The study has also found that the mutation of IDH1 had made glioma cells less aggressive. When implanted into mouse brain the division of the cells at lower rate were much likely to increase the tumor growth.
According to the research, the presence of IDH1 mutations along with the mutations in TP53 and ATRX genes leads to the resistance of the tumor to ionizing radiation. This treatment often damages DNA while killing the cells.
Further research suggested that IDH1 changes it’s activity due to disease-causing mutation. Due to this, a series of chemical reactions get started that modify the cancer cell’s genes in a way that it tends to increase the production of a protein which can repair damaged DNA.
Dr. Maria G. Castro, professor of neurosurgery at Michigan Medicine and a senior 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, program director, NIH’s National Institute of Neurological Disorders and stroke, 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.”
By this study, the researchers have formulated and experimented a new combination therapy. They discovered that by exposing mice with mutant IDH1 tumors with radiation also while injecting them with anti-cancer drugs to resist the DNA repair, they are able to extend its life.
On the contrary, mice had shown no side effect while being treated with either drugs or radiation individually. Similar findings were seen in human gliomas grown in Petri dishes.