Atypical Teratoid/Rhabdoid Tumor

Atypical Teratoid/Rhabdoid Tumor (AT/RT) is a rare, highly malignant central nervous system (CNS) tumor predominantly affecting infants and young children. Although it accounts for only 1–2% of pediatric brain tumors, AT/RT contributes significantly to childhood brain tumor mortality due to its aggressive behavior and resistance to conventional therapies. The hallmark of AT/RT is the inactivation of the SMARCB1 gene, a critical component of the SWI/SNF chromatin-remodeling complex, leading to widespread epigenetic dysregulation and tumorigenesis. In a minority of cases, SMARCA4 mutations are implicated. Molecular profiling has identified four primary AT/RT subgroups—AT/RT–SHH, AT/RT–TYR, AT/RT–MYC and AT/RT–SMARCA4—each characterized by distinct genetic, epigenetic, and transcriptomic features that influence tumor biology, prognosis, and therapeutic response. Clinically, AT/RT presents with variable neurological symptoms depending on tumor location, and diagnosis relies heavily on immunohistochemical loss of SMARCB1/INI1 expression. Neuroimaging, primarily via MRI, reveals subgroup-specific radiographic features, while emerging biomarkers such as circulating tumor DNA and microRNAs offer promising non-invasive tools for diagnosis and monitoring. Current treatment involves multimodal strategies combining surgery, radiotherapy, and intensive chemotherapy, though therapeutic options are limited by patient age and tumor aggressiveness. Novel targeted therapies, including EZH2 inhibitors, immune checkpoint inhibitors, and CAR-T cell therapies, are under investigation. Despite aggressive treatment, overall survival remains poor (30–40%), with long-term survivors often experiencing significant neurocognitive and endocrine sequelae. Advances in molecular characterization and international collaborative efforts are critical to developing personalized therapies aimed at improving outcomes for this devastating pediatric malignancy.