Deadly brain tumors halted by blocking telomere protein

Glioblastoma brain tumors are notoriously difficult to treat, and the prognosis is poor for people with this type of brain cancer. However, a new study may have discovered a way to halt glioblastoma growth and increase patient survival.

By inhibiting a protein called telomeric repeat binding factor 1 (TRF1), researchers were able to stop the growth and division of murine and human glioblastomas.
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Senior study author Maria A. Blasco, head of the Telomeres and Telomerase Group at the Spanish National Cancer Research Centre (CNIO) in Madrid, Spain, and colleagues recently reported their findings in the journal Cancer Cell.

According to the American Brain Tumor Association, glioblastoma accounts for around 15.4 percent of all primary brain tumors in the United States.

Fast-growing and difficult to treat, glioblastoma is one of the deadliest brain tumors. It is estimated that for people with aggressive glioblastoma who are treated with a combination of temozolomide — a chemotherapy drug — and radiation therapy, the median survival is just 14.6 months.
Blocking TRF1 reduced glioblastoma growth

Glioblastomas develop from star-shaped brain cells called astrocytes. These tumors also contain a subset of cells called glioblastoma stem cells (GSCs), which enable the tumors to regenerate. This is one reason why glioblastoma is so difficult to treat.

The researchers note that stem cells contain high levels of the TRF1 protein. TRF1 is a component of shelterin, which is a protein complex that helps to safeguard telomeres — that is, the protective caps at the end of chromosomes.

Additionally, TRF1 plays a significant role in the tumor-regenerating abilities of GSCs. With this in mind, Blasco and her colleagues sought to determine how blocking TRF1 might influence glioblastoma growth.
The researchers removed TRF1 during the formation of glioblastoma tumors in mouse models. This reduced glioblastoma growth in the rodents and increased their survival by 80 percent.

When the team blocked TRF1 in glioblastomas that had already formed in the mice, the rodents’ survival rose by 30 percent.

On further investigation, the researchers found that blocking the TRF1 protein in glioblastoma tumors caused damage to the DNA of telomeres in GSCs, which prevented these cells from proliferating.