The Role of RAS in CNS Tumors: A Key Player or an Overlooked Oncogene?

This review examines the prevalence, molecular mechanisms, and clinical implications of mutations in Central Nervous System (CNS) tumors, with a particular focus on glioblastoma. We summarize the current understanding of RAS-driven oncogenic pathways, their contribution to tumor progression, and potential therapeutic strategies targeting and its downstream effectors. Although direct mutations are rare in primary CNS tumors, alterations in RAS signaling, such as loss and aberrant receptor tyrosine kinase activation, contribute to malignant progression. Furthermore, emerging evidence links mutations to brain metastases, highlighting their significance in CNS oncology. We also discuss recent clinical trials investigating RAS-targeted therapies, including covalent inhibitors, MEK inhibitors, and novel combination approaches. Given the increasing recognition of RAS pathway alterations in CNS malignancies, further research is needed to elucidate their role in tumor biology and explore targeted therapeutic interventions.