Targeting Glutamine Addiction in Diffuse Intrinsic Pontine Gliomas (DIPGs)
Diffuse intrinsic pontine gliomas (DIPGs) are fatal tumors that most often occur in children younger than 5. DIPGs are inoperable due to their location in the brain. Moreover, they are not very sensitive to current chemotherapy/radiation therapies. Therefore, more than 90% of children with DIPGs die within 1.5 years of diagnosis. It is critical to understand the biology of these tumors to develop effective cures. Cancer cells consume nutrients such as sugar glucose, amino acids and glutamine in vast quantities to support their uncontrolled growth. We have discovered that DIPG tumor cells are addicted to glutamine and use glutamine to not only produce energy but also to modify a protein in the nucleus called histone H3. Histone H3 is central to the pathology of DIPG as more than 80% of these tumors bear histone H3 mutations. We aim to understand how DIPG tumor cells are addicted to glutamine and how DIPG tumor cells use glutamine to drive tumor growth.
Once we have understood this, our goal is to use this knowledge to break glutamine addiction and kill DIPG cells. Our studies will lay the groundwork to develop more effective treatments for these lethal childhood brain tumors.