FDA-Approved FGFR Inhibitors Offer Hope for Treating Rare Pediatric Brain Tumors

Recent research highlights the potential of FDA-approved FGFR inhibitors to combat embryonal tumor with multilayered rosettes (ETMR), a highly aggressive and rare childhood brain cancer. A study conducted by scientists at Dana-Farber Cancer Institute, Boston Children's Cancer and Blood Disorders Center, and the Broad Institute utilized advanced single-cell and spatial analysis techniques to better understand ETMR biology. Published in Nature Cancer, the study reveals that ETMR is driven by the C19MC microRNA cluster, which sustains tumor cells in an immature, highly malignant state. The research team discovered that tumor cells resemble early brain development stages, creating a hierarchy of stem-like and neuron-like cells that work together to promote tumor growth. Critical to this process are receptor-ligand interactions involving FGFR and NOTCH pathways, which are active in proliferating neural stem cell–like cells supplied with signals by more differentiated malignant cells. Targeting these interactions with existing FDA-approved FGFR inhibitors, which have already demonstrated early effectiveness in compassionate-use cases, could represent a significant therapeutic breakthrough. Experts emphasize that disrupting tumor cell communication may be key to halting ETMR progression. The findings also suggest promising avenues for antisense therapies against C19MC microRNAs, paving the way for more effective, targeted treatments for this devastating disease. Further clinical trials are necessary to validate the efficacy of FGFR and NOTCH inhibitors and improve outcomes for children affected by ETMR.