The first effective therapy against glioblastoma achieved by attacking telomeres

The Telomere and Telomerase Group at the Spanish National Cancer Research Centre (CNIO) has shown that it is possible to block the growth of human and murine glioblastoma in mouse models by blocking the TRF1 protein, an essential component of the telomere-protective complex known as shelterin. The study, published in Cancer Cell, describes a new and promising way to combat this type of brain tumour, considered one of the most lethal and difficult to treat, by attacking its ability to regenerate and divide immortally.

The average life expectancy of patients with is about 14 months. This common brain can evade and overcome the limited therapeutic options that exist today to treat it. It is particularly known for its ability to regenerate, as the tumour contains a subset of cells with characteristics that are similar to stem cells, called glioblastoma stem cells (GSCs). One of these cells is capable of reproducing the entire tumour.

These GSCs cells are the cornerstone of glioblastoma and one of its identifying features. One of their characteristics is that they have very high levels of the telomeric protein TRF1, which in addition to being essential for protecting telomeres, is required to maintain the capacity of these cells to regenerate the tumour.

“We know that TRF1 is largely expressed in stem cells, so we thought it would be interesting to see what would happen in tumours that had a strong tumour stem cell nature if we blocked TRF1,” explains Maria A. Blasco, head of the Telomeres and Telomerase Group and senior author of the paper. Glioblastoma is clearly a type of tumour that could benefit from blocking TRF1 owing to the ability of its glioma stem cells to regenerate the tumours after current treatments.

“The first thing we saw was that TRF1 is highly overexpressed in both mouse and…

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