New Genetic Drug Targets Discovered for the Aggressive Brain Tumor GBM

The brain tumor described as “aggressive” because it grows rapidly and almost always recurs despite standard treatment, glioblastoma (GBM), has so far had no effective genetically targeted treatments or immunotherapies approved. However, a newly published study identified more than 200 genes associated with GBM and emphasized that some could be targets for new drugs.

Researchers at the Wellcome Sanger Institute and Addenbrooke’s Hospital investigated a well-known cancer gene called EGFR. They designed a new mouse model to show how its mutation initiates glioblastoma and worked with more than 200 genes associated with GBM. Among these, they identified genes that assist EGFR in tumor growth.

- Related topic: Genetic Alterations and Cancer! What Does It Mean for Cancer to Be Genetic?

On July 30, 2020, Genome Biology published the results, opening new avenues for cancer researchers seeking treatments for this challenging brain tumor.

Manage preferences to view external content

Manage preferences to view external content

New targeted therapies and immunotherapies are being developed for patients with glioblastoma, but none has so far been approved, including a targeted drug or immunotherapy. The causes and mechanisms of glioblastoma development are also not clearly understood.

This new study showed that EGFR (epidermal growth factor receptor), a well-known cancer gene, can initiate brain tumor growth on its own in mice, producing tumors highly representative of human glioblastomas. It also identified new genes that potentially need further investigation as targets for treatment.

To identify genes that help EGFR drive cancer, the team used the PiggyBac transposon technique to reveal mutations by inserting a small piece of DNA into different parts of the genome. This uncovered changes in genes working with EGFR to drive brain tumor growth, including tumor-suppressor genes with more than 200 known and new mutations. Many offer new drug targets.

The team compared the results with genome sequences from patients with glioblastoma and discovered many genetic mutations shared by humans and mice. Available human genomic data contain many mutations found in glioblastoma, but which mutations drive the cancer is not clearly understood.

With this new mouse model, the team provides insight into which mutations should be prioritized when developing future drugs.

In conclusion, glioblastoma tumors may be highly resistant to treatments targeting particular molecules because many other genetic drivers can take over and maintain the cancer. New targeted treatments are therefore urgently needed for patients with GBM. Studies like this shed light on the genetic foundations of GBM and pave the way for the desired targeted therapies.