Study Reveals What Makes Brain Cancer Cells Resistant to Treatment

A diagnosis of glioblastoma, a fast-growing type of brain cancer, is devastating for patients and their families, as no cure is available and patients survive for only a median of 15 months.

A team led by investigators at Massachusetts General Hospital (MGH) has now uncovered a mechanism used by glioblastoma cells to become aggressive and resistant to chemotherapy and radiation.

Targeting this mechanism may therefore make the cells susceptible to anti-cancer treatments, which could allow patients to live longer.

The research, which is published in Advanced Biosystems, draws on the knowledge that glioblastoma is not just one entity: different subtypes of glioblastoma cancer cells can be found in a single tumor, and sometimes a less aggressive subtype can transform into a more aggressive one.

Because extracellular vesicles (EVs), which are tiny pouches secreted by every cell of the body, carry various messages from one cell to another, the investigators wondered whether EVs are involved in this transformation.

"We found that the more aggressive and treatment-resistant glioblastoma cells secrete EVs that are taken up by less aggressive glioblastoma cells that in turn grow faster and become treatment resistant," said senior author Bakhos A. Tannous, PhD, Director of the Experimental Therapeutics Unit at Mass General and an Associate Professor of Neurology at Harvard Medical School.

The findings suggest that blocking EVs from moving between aggressive and less aggressive glioblastoma cells may help slow the spread of a tumor and make it more responsive to treatments such as chemotherapy and radiation.

"We also uncovered the pathway triggered in the less aggressive cells upon receipt of EVs from aggressive cells, which may allow us to potentially develop additional anti-glioblastoma therapies," said Markus Schweiger, MS, a graduate student in Dr. Tannous' Lab and the lead author of the study.

In addition, Dr. Tannous noted that the team's findings indicate that research into the potential role of EVs in treatment resistance and tumor progression in other cancer types is also warranted.

Paper cited: Schweiger, M. W., Li, M., Giovanazzi, A., Fleming, R. L., Tabet, E. I., Nakano, I., Würdinger, T., Chiocca, E. A., Tian, T., & Tannous, B. A. (2020). Extracellular Vesicles Induce Mesenchymal Transition and Therapeutic Resistance in Glioblastomas through NF-κB/STAT3 Signaling. Advanced biosystems, e1900312. Advance online publication.

Funding: This work was supported by grants from the National Institutes of Health, the National Cancer Institute, and the National Institute of Neurological Disorders and Stroke.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2019, Mass General was named #2 in the U.S. News & World Report list of "America’s Best Hospitals."