Epigenetic therapies to concurrently target DIPG tumor cells and harness the immune system
Our research project will investigate the association of a very frequent mutation in DIPG tumor cells with proteins that help to establish the structure of DNA. Elevated expression of these proteins seems to affect the normal function of DNA and may result in abnormal cell growth. Our goal is to inhibit these DNA proteins to specifically target the potential cause contributing to the maintenance of DIPG cells. Overall, we expect that elimination of these DNA proteins will result in a greater effect in terms of reducing aberrant DIPG cell growth, tumor progression and activate the immune system. We then will leverage this knowledge to a developed drug that reduces these DNA proteins. We will test if this drug kills DIPG cells in animal models. Our work is important and impactful as our result will lay the groundwork to develop effective therapies for DIPGs.
Project Goals:
First, we plan to test how DIPG tumor cells increase specific proteins that help to establish the structure of DNA. Then, we will use drugs to target this specific protein in tumor cells to see if this drug kills tumor cells. Finally, we will test this drug in pre-clinical animal models to establish therapeutic efficacy.
Project Update 2024:
Brain cancer is currently the most frequent and deadliest type of pediatric tumor. DMGs including DIPG carries an especially fatal prognosis and more than 90% of patients die within 1.5 years of diagnosis. There are no effective treatment options at present and most regimens used in adults or other types of childhood cancers either produce no effect or only marginally
ameliorate survival for DIPG patients. There is therefore an urgent and unmet need for effective therapies for children facing DIPG. Recent sequencing advances have revealed a highly recurrent mutations in a protein called histone H3 80% of DMGs. Our work aim to understand how this H3 mutation changes DNA in tumor cells to help them grow and suppress the immune system. Once we map these pathways, our goal is to reverse these changes in DNA to kill DIPG tumor cells.
