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 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.
Project Update - June 2020
The Venneti Laboratory would like to express their profound and heartfelt thanks to Alex’s Lemonade Stand Foundation and Storm the Heavens Foundations for supporting our efforts and joining hands with us in our battle against childhood brain cancers. Amongst childhood brain tumors, DIPGs are fatal with no effective therapies. To treat these tumors, we need to understand their biology. We propose to address this urgent need by studying changes in how DIPG cells consume nutrients such as the amino acid glutamine to help them proliferate and survive. During the past year, we made significant progress as we have identified that the amino acid glutamine is required for the survival of aggressive DIPG tumor cells. Moreover, we have discovered that glutamine can regulate changes in the nucleus important for the growth of DIPG cells. During the rest of the funding period, we aim to carefully dissect out (a) how do DIPG tumor cells use glutamine to help them grow and (b) develop therapies to suppress glutamine addiction to kill DIPG tumor cells.