Researchers have identified the gene mutation that leads to the brain cancer glioblastoma.

Glioblastomas are malignant and aggressive tumors in the brain. They are difficult to treat because they are made of up different types of cells, and not all cells respond to the same treatments. In addition, they have tentacle-like areas that project into the brain that are difficult to remove.

Research conducted at the University of California, San Francisco may, however, lead to the development of drugs that can target the mutations driving the growth of glioblastomas. They have identified how the common mutation in the telomerase reverse transcriptase (TERT) gene regulator gives these cancer cells the ability to divide and spread indefinitely. 

The TERT gene is one of two genes that encode telomerase, an enzyme that gives stem cells the ability to divide continuously. In many cancers, telomerase is activated through TERT mutations. In the case of glioblastomas, the researchers found that the GABP-b1L subunit of a subunit of GA-binding protein (GABP) activates mutant promoters.

To date, developing drugs that target telomerase has been unsuccessful as they often suffer from undesirable off-target effects. The identification of the GABP-b1L subunit provides an alternative target. The UCSF researchers have formed the company Telo Therapeutics and, in partnership with GlaxoSmithKline, are researching the development of drugs that target GABP-b1L. They hope to find small-molecule inhibitors of GABP-b1L that can be used initially for the treatment of glioblastomas, and ultimately other cancers.