Preclinical evaluation and translational consequences of EZH2-inhibition in malignant brain tumors

Introduction: Medulloblastoma (MB) and glioblastoma (GBM) belong to the most common malignant brain tumors in children, comprising distinct molecular and clinical entities, with in parts widely differing clinical outcomes. Recent sequencing efforts revealed that many mutations found in brain tumors impact chromatin-modifying functions. One of the processes targeted is histone methylation, in particular methylation on histone H3 at lysine 27 (H3K27) implemented by the polycomb repressive complex 2 (PRC2). Enhancer of zeste homolog 2 (EZH2) is a core component of PRC2, catalyzing trimethylation at H3K27. We here e…