From genotype to outcome in optic pathway gliomas: Biology, biomarkers, targeted therapy, and future directions

Optic pathway gliomas (OPG) are a heterogeneous group of low-grade tumors that primarily affect the pediatric population and are frequently associated with neurofibromatosis type 1. Although typically low-grade, OPG can exhibit highly variable clinical behavior, ranging from asymptomatic lesions to progressive visual and neurological impairment. Recent advances in molecular biology have identified key alterations in the Mitogen-Activated Protein Kinase (MAPK) pathway, particularly involving BRAF, such as BRAF^V600E variant and KIAA1549::BRAF fusions, which play a central role in tumor initiation and progression of this kind of tumors. This review synthesizes current evidence on the epidemiology, classification, molecular pathogenesis, and tumor microenvironment of OPG, emphasizing the relationship between genotype and clinical phenotype. Additionally, it examines conventional and emerging therapeutic strategies, including chemotherapy, radiotherapy, and targeted therapies such as MEK and BRAF inhibitors. Understanding the molecular drivers and immune interactions underlying OPG has enabled the development of more precise diagnostic and therapeutic approaches. However, significant gaps remain in understanding the mechanisms of progression, treatment resistance, and genotype-phenotype correlations. Future research should focus on integrating molecular biomarkers into clinical decision-making and exploring combination therapies to improve patient outcomes.