Gene targeting helps overcome the resistance of brain cancer to therapy

August 17, 2020

New insight into a gene that controls energy production in cancer stem cells could help in the search for a more effective treatment for glioblastoma. A McGill-led study published in Nature Communication reveals that suppressing the OSMR gene can improve the effectiveness of radiation therapy.

This approach, led by the laboratory of Arezu Jahani-Asl, Assistant Professor of Medicine at McGill University, was successful in preclinical mouse models where the deletion of the OSMR gene resulted in a significant improvement of tumour response to therapy and expanded lifespan.

Glioblastoma is the most common and aggressive cancerous brain tumour in adults due to its resistance to therapy. Treatment usually involves surgery, followed by chemotherapy and radiation therapy. Despite these intensive efforts, in most cases tumour cells regrow after treatment and the cancer recurs.

Starving cancer stem cells

Glioblastoma tumours contain rare cancer stem cells responsible for therapeutic resistance and tumour regrowth. In the study, researchers uncover the unique role OSMR plays in fortifying cancer stem cells' resistance to therapy by strengthening mitochondria, the powerhouse of cell energy production. It makes the long journey to the mitochondria and interacts with energy-producing machineries to force them to generate more energy for cancer cells.

"To improve patient response to glioblastoma treatment, we must find new vulnerabilities in cancer stem cells and overcome their resistance to therapy. By suppressing OSMR, we were able to halt energy production in cancer stem cells, essentially starving them to death," says Jahani-Asl.

The study provides evidence that targeting OSMR gene, in combination with radiation therapy, can pave the way for future clinical trials that better treat glioblastoma tumours. The next step is to leverage these tools into a clinical trial, the researchers say.
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About the study

"OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation" by Ahmad Sharanek, Audrey Burban, Matthew Laaper, Emilie Heckel, Jean-Sebastien Joyal, Vahab D. Soleimani, and Arezu Jahani-Asl is published in Nature Communication. The study was supported by CIHR and The Brain Tumor Charity.

DOI: http://dx.doi.org/10.1038/s41467-020-17885-z

About McGill University

Founded in Montreal, Quebec, in 1821, McGill University is Canada's top ranked medical doctoral university. McGill is consistently ranked as one of the top universities, both nationally and internationally. It?is a world-renowned?institution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. McGill attracts students from over 150 countries around the world, its 12,800 international students making up 31% of the student body. Over half of McGill students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue.

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