Stephen C. Mack, Ph.D., Baylor College of Medicine, Texas Children’s
one-year study, final summary
We are grateful for support provided by the CBTF and funders that have allowed us to pursue our project on the characterizing “The Role of MOS Proto-Oncogene in H3.3K27M Diffuse Intrinsic Pontine Glioma”. Diffuse intrinsic pontine glioma (DIPG) remains a fatal diagnosis with few experimental therapies available to patients in clinical trials. Advancements are desperately needed to improve our understanding of the molecular basis of DIPG to develop safe and effective treatments. Through work funded by CBTF in the past year we were able to make several key findings: 1) That a protein called MOS is highly essential for DIPG tumor cell growth, and 2) MOS and other related genes and transcripts can be inhibited by drugs called bromodomain inhibitors.
An exciting extension of our work on MOS was an unexpected finding that other transcripts, outside genes, called endogenous retroviruses were also activated. This led us to a new idea that targeting both genes and viral transcripts could be an effective therapeutic approach, which is work we published in May 2019, in a journal called Cancer Cell. Our findings have also shed insight into the biology of other aggressive pediatric brain tumors such as ependymoma. Importantly, these findings as a result of CBTF funding have now led to a clinical trial proposal to the pediatric brain tumor consortium as a novel therapy for children with DIPG and ependymoma.
Basic research on brain tumors is an area currently in desperate need for advancements that can help establish and guide clinical trials. Unfortunately, brain tumor research, particularly in children remains a topic that is under-funded, thus posing a challenge for researchers entering the field; as a result, a lack of progress on new treatments for patients. For our lab, CBTF has provided the investment needed to launch a project in an area of high clinical need, yet few available resources to obtain pre-clinical data. We have now used this funding and foundational research to apply for additional resources through the National Institutes of Health.