Therapeutic Targets and Molecular Mechanisms in Childhood Brainstem Tumors
Lay Summary: Diffuse Intrinsic Pontine Gliomas, (DIPGs), are aggressive and deadly brain tumors that occur in children. These tumors are located in the brainstem. Currently, there is no treatment for DIPGs, and patients invariably succumb to the disease. To find ways to treat DIPGs, we need to better understand how they arise, and how they become so aggressive.
Project Goal: To do this, I propose to study tumor samples and cell lines that are derived from human DIPGs. I will also develop and analyze mouse DIPG models, because they can be studied in much more details than humans. Throughout these efforts, I will aim to identify components of the DIPG cells that we could target with drugs to kill the tumors. As well, I will be involved in an international effort to develop and test a new kind of drug specifically designed for DIPGs. This research will help us understand how DIPGs occur and how we can treat them, an urgent need for children with these terrible tumors.
Project Update 2022: There is an urgent need to develop new therapies for Diffuse Midline Gliomas (DMGs), a type of brain tumors that occurs mostly in children. To understand how DMGs appear and progress, I analyzed mouse models of the disease, and tumor cells from patients. I generated several new mouse lines that carry mutations that are analogous to those that cause DMGs in humans. In addition, I identified molecules that maintain tumor cell fitness. Some of these molecules could be targeted with drugs, representing potential new therapeutic avenues. Complementing these efforts, I have participated in an open-science initiative to develop and characterize drugs that target one of the roots of DMGs. The tools generated, and the results obtained, will support further investigations of how DMGs arise, progress, and could be treated.
Publications: "Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas" March 2020 in Cancer Cell
