Gliomas are common brain tumors that constitute approximately one third of all cancers of the nervous system. In a study funded by the National Institutes of Health (NIH), researchers tested a novel combination treatment approach on mice with tumors with characteristics similar to human astrocytomas--a type of slow-growing glioma--and found tumor regression in 60 percent of the mice treated. These encouraging results, published online on December 17, 2020 in the Journal of Clinical Investigation, could be the first step toward developing a treatment for this type of brain cancer. The open-access article is titled “Inhibition of 2-Hydroxyglutarate Elicits Metabolic Reprogramming and Mutant IDH1 Glioma Immunity in Mice.” Led by senior authors Maria Castro, PhD, and Pedro Lowenstein, MD, PhD, together with a team of researchers at the University of Michigan Rogel Cancer Center in Ann Arbor specifically tested inhibitors of the compound D-2-Hydroxyglutarate (D-2-HG), which is produced by cancer cells, on a mouse version of astrocytoma carrying mutations in the genes IDH1 and ATRX, along with an inactivated form of the tumor suppressor protein 53 (TP53) gene. When the implanted mice were treated with a drug to block the production of D-2-HG along with standard of care radiation and temozolomide (chemotherapy) treatments, their survival significantly improved. Looking more closely at tumor cells grown in dishes, the researchers saw that blocking D-2-HG caused the cells to become more susceptible to radiation treatment. However, the treatment also increased the amount of an "immune checkpoint" protein, which tumors use to turn off T cells and evade the immune system.
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