Researchers have pinpointed the MERTK receptor tyrosine kinase as a potential drug target for ZFTA-RELA fusion-positive ependymomas, aggressive pediatric brain cancers with extremely poor survival rates. Using systems-level analysis combining human tumor gene expression data with genetically engineered models, the team demonstrated that MERTK inhibition could disrupt tumor cell survival pathways specific to this cancer subtype. This finding represents a significant advance for a malignancy that currently has no targeted treatment options and typically proves fatal within two years of diagnosis. The MERTK pathway has emerged as increasingly important across multiple cancer types, particularly in promoting tumor cell survival and resistance to cell death. However, targeting MERTK specifically in pediatric brain tumors remained unexplored until this work. The systems biology approach—integrating large-scale human tumor data with laboratory models—provides a robust framework for identifying vulnerabilities that might be missed by traditional single-gene studies. For families facing this devastating diagnosis, MERTK-targeted therapies could offer the first molecularly-informed treatment strategy. The challenge now lies in developing brain-penetrant MERTK inhibitors suitable for pediatric use, as existing compounds may not effectively cross the blood-brain barrier or may carry unacceptable toxicity profiles for children.