Fighting brain cancer at its root

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Sagittal MRI with contrast of a glioblastoma WHO grade IV in a 15-year-old boy. Credit: CC BY 2.5 - Christaras A

McGill University researchers identify proteins that drive cancer stem cells. Targeting and suppressing a particular protein called galectin-1 could provide a more effective treatment for glioblastoma, in combination with radiation therapy.

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.

According to the researchers, no matter how low the weeds are cut, if the roots are not pulled out, the weeds will just grow back.

Getting to the root of the problem

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, say the researchers. By targeting the way the cells operate, they discovered a new way to disrupt the production of new tumors.

“What we found was really astonishing for us. After we inhibited the galectin-1 protein, the brain tumors simply didn’t grow for several months,” says Arezu Jahani-Asl, 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 a protein called galectin-1 interacts with another protein called HOXA5 to control the genetic programs that drive cancer stem cell behavior. By suppressing galectin-1 in preclinical models, they found a significant improvement in tumor response to radiation therapy, resulting in expanded lifespan.

The researchers also analyzed patient databases and found that glioblastoma patients with low expression of galectin-1 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.

Paving the way for new therapies

The discovery sheds light on the mechanisms that regulate cancer stem cells. The findings provide evidence that targeting galectin-1 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 galectin-1 and HOXA5 complex in the brain, with advances in gene therapy through CRISPR technology.

About this study

“Transcriptional Control of Brain Tumour Stem Cells by a Carbohydrate-Binding Protein” by Ahmad Sharanek, Audrey Burban, Aldo Hernandez Corchado, Ariel Madrigal, Idris Fatakdawala, Hamed Shateri Najafabadi, Vahab D Soleimani, and Arezu Jahani-Asl was published in Cell Reports.


Source:

Materials provided by McGill University. Content may be edited for clarity, style, and length.


 

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