Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas
Jérôme Fortin, Ruxiao Tian, Ida Zarrabi, Graham Hill, Eleanor Williams, Gonzalo Sánchez‐Duffhues, Midory Thorikay, Parameswaran Ramachandran, Robert Siddaway, Jong Fu Wong, Annette Wu, Lorraine N. Apuzzo, Jillian Haight, Annick You-Ten, Bryan E. Snow, Andrew Wakeham, David J. Goldhamer, Daniel Schramek, Alex N. Bullock, Peter ten Dijke, Cynthia Hawkins, Tak W. Mak
Abstract
upregulates transcription factors which control differentiation and DIPG cell fitness. Furthermore, we characterize E6201 as a dual inhibitor of ACVR1 and MEK1/2, and demonstrate its efficacy toward tumor cells in vivo. Collectively, our results describe an oncogenic mechanism of action for ACVR1 mutations, and suggest therapeutic strategies for DIPGs.
Topics & Concepts
CarcinogenesisGliomaMutantBiologyCancer researchMedicineNeuroscienceGeneticsCancerGeneGlioma Diagnosis and TreatmentRenal and related cancersRNA Research and Splicing