Atypical Teratoid Rhabdoid Tumor: Current Therapy and Future Directions
Open Access
- 1 January 2012
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Oncology
- Vol. 2, 114
- https://doi.org/10.3389/fonc.2012.00114
Abstract
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 three 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 three 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 anectdotal 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.Keywords
This publication has 65 references indexed in Scilit:
- A remarkably simple genome underlies highly malignant pediatric rhabdoid cancersJCI Insight, 2012
- Sequencing of Local Therapy Affects the Pattern of Treatment Failure and Survival in Children With Atypical Teratoid Rhabdoid Tumors of the Central Nervous SystemInternational Journal of Radiation Oncology*Biology*Physics, 2012
- Histone deacetylase inhibition decreases proliferation and potentiates the effect of ionizing radiation in atypical teratoid/rhabdoid tumor cellsNeuro-Oncology, 2011
- p16INK4Aand p14ARFTumor Suppressor Pathways Are Deregulated in Malignant Rhabdoid TumorsJournal of Neuropathology and Experimental Neurology, 2011
- The rexinoid bexarotene represses cyclin D1 transcription by inducing the DEC2 transcriptional repressorBreast Cancer Research and Treatment, 2010
- Aurora Kinase Inhibitors - Rising Stars in Cancer Therapeutics?Molecular Cancer Therapeutics, 2010
- Initial testing of the aurora kinase a inhibitor MLN8237 by the Pediatric Preclinical Testing Program (PPTP)Pediatric Blood & Cancer, 2010
- High-dose chemotherapy and autologous stem cell rescue for atypical teratoid/rhabdoid tumor of the central nervous systemJournal of Neuro-Oncology, 2009
- Nordihydroguaiaretic acid, a cytotoxic insulin-like growth factor-I receptor/HER2 inhibitor in trastuzumab-resistant breast cancerMolecular Cancer Therapeutics, 2008
- Novel role for insulin as an autocrine growth factor for malignant brain tumour cellsBiochemical Journal, 2007