Atypical teratoid
rhabdoid tumors (ATRTs) are rare
central nervous system tumors that comprise approximately 1-2% of all pediatric
brain tumors; however, in patients less than 3 years of age this
tumor accounts for up to 20% of cases. ATRT is characterized by loss of the long arm of chromosome 22 which results in loss of the hSNF5/INI-1 gene. INI1, a member of the SWI/SNF chromatin remodeling complex, is important in maintenance of the mitotic spindle and cell cycle control. Overall survival in ATRT is poor with median survival around 17 months. Radiation is an effective component of
therapy but is avoided in patients younger than 3 years of age due to long term neurocognitive sequelae. Most long term survivors undergo
radiation therapy as a part of their upfront or
salvage therapy, and there is a suggestion that sequencing the radiation earlier in
therapy may improve outcome. There is no standard curative chemotherapeutic regimen, but anecdotal reports advocate the use of intensive
therapy with
alkylating agents, high-dose
methotrexate, or
therapy that includes high-dose
chemotherapy with stem cell rescue. Due to the rarity of this
tumor and the lack of randomized controlled trials it has been challenging to define optimal
therapy and advance treatment. Recent laboratory investigations have identified aberrant function and/or regulation of
cyclin D1,
aurora kinase, and
insulin-like growth factor pathways in ATRT. There has been significant interest in identifying and testing therapeutic agents that target these pathways.