Mouse study suggests new approach to treat common type of glioma

Gliomas are common brain tumors that make up about a third of all cancers of the nervous system. In a study funded by the National Institutes of Health (NIH), researchers tested a new combination treatment approach in mice with tumors with features similar to human astrocytomas – a type of slow-growing glioma – and found a tumor regression in 60% of cases. treated mice.

These encouraging results, published in the Clinical investigation journal, could be the first step towards developing a treatment for this type of brain cancer.

Led by lead authors Maria Castro, Ph.D. and Pedro Lowenstein, MD, Ph.D. with a team of researchers from the University of Michigan Rogel Cancer Centerb in Ann Arbor specifically tested inhibitors of the compound D-2-Hydroxyglutarate (D-2-HG), which is produced by cancer cells, on a murine version of astrocytoma carrying mutations in the IDH1 and ATRX genes, as well as an inactivated form of the tumor suppressor protein gene 53 (TP53) .

When the implanted mice were treated with a drug to block the production of D-2-HG along with standard radiotherapy and temozolomide (chemotherapy) treatments, their survival improved dramatically. Taking a closer look at the tumor cells grown in dishes, the researchers found that blocking D-2-HG made the cells more sensitive to radiation therapy. However, the treatment also increased the amount of an “immune checkpoint” protein, which tumors use to deactivate T cells and evade the immune system.

Inhibiting this immune checkpoint protein with additional medication resulted in an even greater improvement in survival, as the mouse’s immune system was able to attack the tumor.

Importantly, this combination therapy also led to immunological memory against the glioma, which means that the mouse now had T cells adapted to the specific tumor. Because gliomas almost always grow back after treatment, these T cells make the animal better prepared to repel regrowth.

It should be noted that these experiments were carried out in mice. Nevertheless, the preclinical results produced by this combination therapy could represent a key advance in the development of an improved treatment regimen, which combines D-2-HG and inhibition of immune checkpoints, radiation and temozolomide, for patients with astrocytomas.