Various antitumoral targets identified from an unbiased multiomics screen on H3K27M mutated Diffuse Midline Glioma patient-derived material.

We are finalizing target validation and developing high throughput small molecule screening assays to develop novel compounds that can be used to treat this devastating childhood cancer.

Technology:

Diffuse Midline Glioma (DMG, also known as Diffuse Intrinsic Pontine Glioma) is an aggressive, paediatric brainstem tumour primarily arising in the pons area of the brain, responsible for important vital functions. This is an extremely fatal disease with an average diagnosis between the ages of 6-8 and a mortality rate of 99%. Sadly, most children will die within a year of diagnosis and the survival rate after 5 years is <1%. This is primarily due to a lack of effective treatments and, despite over 100 clinical trials conducted to investigate a range of treatments, the prognosis remains dismal. Therefore, solutions which can address this unmet need are urgently needed.

To address this, researchers at the CRG have identified downstream, antitumoral targets associated with mutations in histone H3, a key onco-histone driver of over 80% of the DMG cases. Current efforts are focused on validating these targets, develop a screening assay and beginning work on hit identification in the course of 2024 and early 2025.

Advantages:

In contrast to the only available therapy, radiation therapy (which only gives temporary effects), which generally damages the DNA of cancerous tissue, targeting such specific H3 mutation-triggered vulnerabilities, would address specific DMG-driving events.​