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Fighting brain cancer at its root

MONTREAL (QUE), CA, September 2021 — Due to its resistance to therapy, glioblastoma is the most common and aggressive cancerous brain tumor in adults. It grows fast and spreads quickly. While treatments such as surgery, radiation and chemotherapy can help ease symptoms for a few months, in most cases tumor cells regrow after treatment and the cancer recurs.

Among all cancerous cells, some act as stem cells that reproduce themselves and sustain the cancer, much like normal stem cells typically renew and sustain our organs and tissues. By targeting the way the cells operate, researchers at McGill University have discovered a new way to disrupt the production of new tumors.

They discovered that a protein called galectin1 interacts with another protein called HOXA5 to control the genetic programs that drive cancer stem cell behavior. By suppressing galectin1 in preclinical models, they found a significant improvement in tumor response to radiation therapy, resulting in expanded lifespan.

“What we found was really astonishing for us. After we inhibited the galectin1 protein, the brain tumors simply didn’t grow for several months,” said Arezu Jahani-Asl, Ph.D., an associate professor of medicine at McGill University. “To improve patient response to therapy, we must exploit these newly identified vulnerabilities in cancer stem cells.”

The researchers also analyzed patient databases and found that glioblastoma patients with low expression of galectin1 and HOXA5 proteins had the best prognosis. Together, these proteins along with another called STAT3 activate mechanisms that promote a particularly aggressive type of glioblastoma.

The discovery sheds light on the mechanisms that regulate cancer stem cells. The findings provide evidence that targeting galectin1 protein, in combination with radiation therapy, can pave the way for future clinical trials to treat glioblastoma tumors.

The next step is to compare the effectiveness of different approaches to suppressing the galectin1 and HOXA5 complex in the brain, with advances in gene therapy through CRISPR technology.

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DOI: 10.1016/j.celrep.2021.109647