The study focused on diffuse midline gliomas (DMGs), a group of difficult-to-treat tumors that includes diffuse pons glioma (DIPG) - a rare and fatal brain cancer that affects children, with an average survival rate of no more than 12 months.
"We know that no single drug can single-handedly eliminate the most aggressive forms of brain cancer," said Maria Tsoli, an associate professor at the University of New South Wales, explaining that this prompted the team to explore the possibility of combining treatments to achieve better results.
Professor David Ziegler explained that one of the biggest challenges with these tumors is the activation of thousands of genes at the same time, which fuels cancer growth, adding: "It has proven extremely difficult to find a way to stop them all."
The two drugs used belong to a new generation of medicines known as epigenetic therapies, which control how genes are turned on and off without changing the DNA itself, by interfering with the transcription process that produces proteins inside cells.
Dr. Holly Holliday, a lecturer at the University of New South Wales and the study's first co-author, said: "We discovered a promising combination of drugs that successfully halts the transcription process, disabling thousands of genes at once."
The study focused on two key transcription proteins, FACT and BET, which are found in high concentrations in cancer cells. Although drugs that inhibit each protein individually exist, their effect on their own has been limited. However, when the two drugs were used together, cancer cells died in laboratory experiments, and the treatment slowed tumor growth in mice and extended their lifespan.
The results also showed that the treatment activates signals associated with the immune system, which may facilitate targeting cancer cells. Therefore, the researchers believe that combining this treatment with immunotherapies such as CAR-T cell therapy could enhance its effectiveness in the future.
The study provides initial evidence of the idea's potential, but further research is needed before clinical application. Dr. Amina Khan, a lecturer at the University of New South Wales and the study's first co-author, explained that both types of drugs are currently under development for human use, undergoing ongoing clinical trials. She added, "The FACT protein inhibitor, known as CBL0137, has been tested on children and the results have demonstrated its safety."
The next phase will focus on identifying the best BET protein inhibitor to use with CBL0137, in preparation for a clinical trial for children, opening up prospects for treating brain tumors in children.
