Halting the ‘immortality’ mechanism in glioblastomas

Friday 14 September 2018

A team of researchers have identified a new therapeutic target in glioblastoma cells that could halt the aggressive growth of this tumour type

Glioblastoma is a highly lethal type of primary brain tumour and has a high rate of recurrence despite patients undergoing surgery, radiation, and chemotherapy.

Glioblastomas affect 2,200 individuals in the UK annually making it essential to investigate the various mechanism of tumour growth and survival.

In contrast to healthy cells, which are strictly limited in the number of times they are able to divide, glioblastoma cells have the ability to divide indefinitely.

This ability to replicate and become 'immortal' is a result of a mutation in a gene called TERT.

TERT is responsible for activating an enzyme (a type of protein) called telomerase that helps repair and rebuild telomeres.

Telomeres are protective caps that sit at the ends of chromosomes and shorten each time a cell divides.

Once the telomeres become too short and can no longer protect the DNA, it is a signal that the cell cannot divide anymore and has reached the end of its lifespan.

Thus, cancer cells with mutated TERT genes activate telomerase, allowing them to rebuild the telomeres and divide indefinitely.

Previous research has found that drugs to block telomerase are too toxic for patients. However, researchers at UC San Francisco have found another method to block telomerase.

The study, led by Professor Joseph Costello, found that blocking GABP, a protein involved in the regulation of the TERT gene, prevented the activation of telomerase and slowed glioblastoma cell division.

“In theory what we have now is a therapeutic target that is not TERT itself, but a key to the TERT switch that is not essential in normal cells,” said Professor Costello.

“Now we have to design a therapeutic molecule that would do the same thing.”

While further research is required to confirm these results, these findings will have significant impact on future treatments as the researchers have identified a new therapeutic target that has the potential to slow down tumour growth.

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