Multi-omics Dissection of MAPK-driven Senescence Unveils Therapeutic Vulnerabilities in KIAA1549::BRAF-fusion Pediatric Low-Grade Glioma Models

This study investigates molecular mechanisms regulating oncogene-induced senescence (OIS) and senescence-associated secretory phenotype (SASP) in pediatric low-grade gliomas (pLGGs). Using multi-omics analysis of a pilocytic astrocytoma cell line, we identified key OIS effectors and pathways affected by MAPK inhibition. We constructed a network of MAPK-OIS-SASP interdependencies, revealing potential therapeutic targets. Several compounds targeting signaling nodes were identified and validated, suggesting new treatment strategies for pLGGs.