Genetic Finding Reveals Potential New Glioblastoma Treatment

Glioblastoma brain cancer, CT scan

Researchers at McGill University report they have identified proteins that drive cancer stem cells and have observed that targeting and suppressing the protein galectin1 may provide a more effective treatment for glioblastoma, in combination with radiation therapy, than current therapy options.

Glioblastoma is an aggressive type of cancer that can occur in the brain or spinal cord. It forms from cells called astrocytes that support nerve cells. Glioblastomas display cellular heterogeneity, with stem-like glioblastoma cells at the apex. Although the original identification of the stem cells dates back more than a decade, the purification and characterization of GSCs remains challenging.

“Brain tumor stem cells (BTSCs) and intratumoral heterogeneity represent major challenges in glioblastoma therapy,” the researchers write in the journal Cell Reports. “Here, we report that the LGALS1 gene, encoding the carbohydrate binding protein, galectin1, is a key regulator of BTSCs and glioblastoma resistance to therapy.”

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

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.

“In conclusion, we report a role for the carbohydrate-binding protein, galectin1, in regulation of glioma stem cells and glioblastoma progression via a cross talk with HOXA5. Our data highlight the importance of galectin1-HOXA5 targeting as a promising approach to deplete malignant cancer stem cells and suppress glioblastoma tumorigenesis,” concluded the researchers.

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