Targeting Early Tumor Drivers to Treat DIPG/DMG

Diffuse midline gliomas (DMGs) are fast-growing and deadly brain tumors that mostly affect children. There are currently no effective treatments for these cancers, and the outlook for patients is very poor.

Scientists and clinicians have discovered that DMGs are caused by specific changes in the DNA, known as mutations. Some of these mutations happen very early in the tumor’s development and are found throughout the cancer. These early mutations may play a key role in starting and growing the tumor. Because they are found in most of the cancer cells, they could be good targets for new treatments. But to know if these treatments could work, we need to find out if these early mutations are still important for keeping the cancer alive later on.

This research project aims to answer that question. Using mouse models and cells taken from patient, we will study how these early mutations affect the cancer over time. In particular, we will focus on a mutation in a molecule called histone 3 (H3), which is found in many cases of DMG. Since there are different types of DMGs with H3 mutations, we will test whether some types respond better than others when H3 mutations are turned off.

In another part of the study, we will look at a different early mutation in a molecule called ACVR1. Our early findings suggest that blocking ACVR1 may make cancer cells more vulnerable to certain drugs. We will now test whether combining ACVR1 blockers with these drugs could be more effective than using either one alone.

Altogether, this research will help us understand whether blocking the earliest mutations in DMG can stop the cancer from growing, and which patients are most likely to benefit. The results could lead to new treatment strategies for this devastating childhood cancer.