{"entity":{"id":"atrt","kind":"cancer","name":"Atypical teratoid/rhabdoid tumour (ATRT)","aka":["AT/RT","Rhabdoid tumour of the CNS","Rhabdoid tumour predisposition syndrome"],"tldr":"ATRT is an aggressive brain tumour of babies and toddlers caused by loss of a single gene, SMARCB1, part of the machinery that opens and closes DNA. Intensive chemotherapy with stem-cell rescue, and radiotherapy where age allows, now cure a meaningful share of children who once had little chance, and drugs aimed at the epigenetic consequence of SMARCB1 loss (EZH2 inhibitors) are in trials.","summary":"Atypical teratoid/rhabdoid tumour is a WHO grade 4 embryonal tumour defined by biallelic inactivation of SMARCB1 (INI1) or, rarely, SMARCA4, both core subunits of the SWI/SNF chromatin-remodelling complex. It is one of the genetically simplest human cancers, often with no other recurrent mutation, yet it splits into three epigenetic subgroups (ATRT-TYR, ATRT-SHH, ATRT-MYC) with different locations, ages and outcomes. About a third of children carry a germline SMARCB1 or SMARCA4 alteration (rhabdoid tumour predisposition syndrome), which matters for siblings and for the risk of synchronous renal or soft-tissue rhabdoid tumours. Median age at diagnosis is under two years, which limits radiotherapy.\n\nFew children survived until intensive multimodal protocols were adopted. The COG trial ACNS0333 combined maximal resection, induction chemotherapy (including high-dose methotrexate), three cycles of high-dose chemotherapy with autologous stem-cell rescue, and focal radiotherapy adapted to age, and reported markedly better survival than historical controls (JCO 2020). The European EU-RHAB registry-based regimen (conventional chemotherapy with intraventricular methotrexate, radiotherapy for older children) gives comparable results and forms the basis of the SIOPE ATRT01 trial. Extent of resection, age, metastatic disease and subgroup all predict outcome.\n\nThe biology points to therapy: loss of SMARCB1 leaves the PRC2 methyltransferase EZH2 unopposed, and the EZH2 inhibitor tazemetostat, already approved for SMARCB1-negative epithelioid sarcoma in adults, has shown responses in children with ATRT and other rhabdoid tumours in a paediatric phase 1 and is being combined with chemotherapy. Other avenues include CDK4/6 inhibition, aurora kinase A inhibitors (alisertib) and the EZHIP-independent dependency on the residual SWI/SNF subunit BRG1. Methylation-based subgrouping is expected to stratify the next generation of trials.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Atypical_teratoid_rhabdoid_tumor","links":[{"label":"NCI PDQ: childhood CNS atypical teratoid/rhabdoid tumour","url":"https://www.cancer.gov/types/brain/hp/child-cns-atrt-treatment-pdq"},{"label":"ACNS0333: intensive multimodal therapy for ATRT (JCO 2020)","url":"https://doi.org/10.1200/JCO.19.01776"},{"label":"EU-RHAB registry outcomes (Neuro-Oncology 2020)","url":"https://doi.org/10.1093/neuonc/noz244"}],"tags":["nci-coverage","paediatric","cns"],"related":["epithelioid-sarcoma","medulloblastoma","wilms-tumor","ependymoma","cns-germ-cell-tumours"],"cancers":[],"sections":[],"technologies":["autologous-stem-cell-transplant","methylation-profiling","proton-therapy","cytotoxic-chemotherapy","germline-testing"],"targets":["ezh2"],"drugs":["tazemetostat","methotrexate","cyclophosphamide","cisplatin","carboplatin","vincristine"],"companies":["childrens-oncology-group"],"institutions":["siop-europe","dkfz","st-jude"],"pathways":["swi-snf-chromatin","epigenetic-reprogramming","hedgehog","myc"],"terms":["hereditary-cancer-syndromes","late-effects"],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-survivorship"],"keyPapers":["paper-fruhwald-neuro-oncol"],"journals":[],"dependsOn":[],"notes":[],"group":"paediatric","burden":"Rare: a small fraction of childhood brain tumours overall, but among the most common malignant brain tumours in infants under one year (NCI PDQ).","subtypes":["ATRT-TYR (infants, infratentorial, melanosomal markers)","ATRT-SHH (supratentorial and infratentorial, SHH and NOTCH signalling)","ATRT-MYC (older children, supratentorial, MYC expression; overlaps with extracranial rhabdoid tumours)","SMARCA4-deficient ATRT (rare, often germline)"],"biomarkers":["Loss of SMARCB1 (INI1) nuclear staining by immunohistochemistry","SMARCB1 or SMARCA4 sequencing, somatic and germline","Methylation subgroup (TYR, SHH, MYC)","Metastatic stage on MRI and cerebrospinal-fluid cytology","Age (radiotherapy eligibility)","Extent of resection"],"standardOfCare":[{"setting":"Newly diagnosed, any age","approach":"Maximal safe resection followed by an intensive multimodal protocol: ACNS0333-style induction, high-dose chemotherapy with autologous stem-cell rescue, and age-adapted focal radiotherapy; or the EU-RHAB regimen with intraventricular methotrexate. Enrolment in SIOPE ATRT01 or a COG successor where available.","refs":["autologous-stem-cell-transplant","methotrexate","cyclophosphamide","cisplatin","carboplatin","vincristine","proton-therapy","acns0333"],"guideline":{"version":"COG ACNS0333 (JCO 2020); EU-RHAB","url":"https://doi.org/10.1200/JCO.19.01776"}},{"setting":"Germline SMARCB1 or SMARCA4 alteration","approach":"Genetic counselling and testing of parents and siblings; surveillance imaging for synchronous or second rhabdoid tumours in the kidney and soft tissue.","refs":["germline-testing"],"guideline":{"version":"NCI PDQ: childhood CNS atypical teratoid/rhabdoid tumour","url":"https://www.cancer.gov/types/brain/hp/child-cns-atrt-treatment-pdq"}},{"setting":"Relapsed or refractory","approach":"Aurora kinase A inhibition and re-irradiation where feasible, with enrolment in a relapse trial the preferred route; EZH2 inhibition with tazemetostat was used in trials and on compassionate grounds until the drug was withdrawn from all markets in March 2026. No regimen is standard at relapse, and symptom and supportive care run alongside from the start.","refs":["tazemetostat","palliative-care"]}],"stateOfArt":["Intensive multimodal therapy (ACNS0333, EU-RHAB) turned ATRT from an infant tumour almost no child survived into one that is cured in a meaningful share of children.","Three methylation subgroups (TYR, SHH, MYC) explain much of the heterogeneity and are being built into trial stratification.","SMARCB1 loss creates an EZH2 dependency; tazemetostat produced responses in paediatric rhabdoid tumours before its 2026 withdrawal, so the dependency is validated but a next EZH2 inhibitor is needed.","Germline testing is routine because a third of children carry a predisposition that affects the whole family."],"history":[{"year":1987,"title":"ATRT described as distinct from medulloblastoma","note":"Rorke and colleagues recognise the rhabdoid tumour of the CNS.","refs":[]},{"year":1998,"title":"SMARCB1 (hSNF5/INI1) identified as the rhabdoid tumour gene","note":"Versteege and colleagues (Nature) find biallelic loss, the first chromatin-remodelling tumour suppressor.","refs":[]},{"year":2016,"title":"Three molecular subgroups defined","note":"Johann and Torchia (Cancer Cell) describe ATRT-TYR, ATRT-SHH and ATRT-MYC by methylation and expression.","refs":["methylation-profiling"]},{"year":2020,"title":"ACNS0333 reports improved survival with intensive therapy","note":"COG phase 3 with high-dose chemotherapy and autologous rescue (JCO 2020).","refs":["autologous-stem-cell-transplant"]},{"year":2020,"title":"Tazemetostat approved for SMARCB1-negative epithelioid sarcoma","note":"First EZH2 inhibitor approval; paediatric rhabdoid tumour responses in the phase 1 programme.","refs":["tazemetostat","ezh2"]}],"pipeline":["methylation-profiling","proton-therapy","pediatric-match"],"openProblems":["Infants too young for radiotherapy and children with metastatic or ATRT-MYC disease still do poorly; SIOPE ATRT01 and COG successors are testing intensified and subgroup-directed therapy.","Long-term neurocognitive and endocrine cost of intensive therapy in the first years of life; proton therapy and radiation-sparing arms aim to reduce it.","Translating the EZH2 dependency into cures: tazemetostat combinations with chemotherapy are in early trials.","Rarity: international registries (EU-RHAB) and shared protocols are the only route to adequately powered trials."],"parent":"brain-tumours"},"route":"/cancers/atrt/","neighbours":{"cancer":[{"id":"brain-tumours","kind":"cancer","name":"Brain and spinal cord tumours (all types)","route":"/cancers/brain-tumours/"},{"id":"cns-germ-cell-tumours","kind":"cancer","name":"Central nervous system germ cell tumours (germinoma and non-germinomatous)","route":"/cancers/cns-germ-cell-tumours/"},{"id":"childhood-cancers","kind":"cancer","name":"Childhood cancers (all types)","route":"/cancers/childhood-cancers/"},{"id":"choroid-plexus-carcinoma","kind":"cancer","name":"Choroid plexus carcinoma","route":"/cancers/choroid-plexus-carcinoma/"},{"id":"ependymoma","kind":"cancer","name":"Ependymoma","route":"/cancers/ependymoma/"},{"id":"epithelioid-sarcoma","kind":"cancer","name":"Epithelioid sarcoma","route":"/cancers/epithelioid-sarcoma/"},{"id":"medulloblastoma","kind":"cancer","name":"Medulloblastoma","route":"/cancers/medulloblastoma/"},{"id":"poorly-differentiated-chordoma","kind":"cancer","name":"Poorly differentiated chordoma (SMARCB1-deficient)","route":"/cancers/poorly-differentiated-chordoma/"},{"id":"wilms-tumor","kind":"cancer","name":"Wilms tumour (nephroblastoma)","route":"/cancers/wilms-tumor/"}],"technology":[{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"methylation-profiling","kind":"technology","name":"DNA methylation profiling","route":"/technologies/methylation-profiling/"},{"id":"palliative-care","kind":"technology","name":"Early integrated palliative care","route":"/technologies/palliative-care/"},{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"}],"target":[{"id":"ascl1","kind":"target","name":"ASCL1","route":"/targets/ascl1/"},{"id":"ezh2","kind":"target","name":"EZH2","route":"/targets/ezh2/"},{"id":"smarcb1","kind":"target","name":"SMARCB1","route":"/targets/smarcb1/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"tazemetostat","kind":"drug","name":"Tazemetostat","route":"/drugs/tazemetostat/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"company":[{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"}],"institution":[{"id":"dkfz","kind":"institution","name":"German Cancer Research Center (DKFZ)","route":"/institutions/dkfz/"},{"id":"siop-europe","kind":"institution","name":"SIOP Europe (European Society for Paediatric Oncology)","route":"/institutions/siop-europe/"},{"id":"st-jude","kind":"institution","name":"St. Jude Children's Research Hospital","route":"/institutions/st-jude/"}],"pathway":[{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"hedgehog","kind":"pathway","name":"Hedgehog signalling","route":"/pathways/hedgehog/"},{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"},{"id":"swi-snf-chromatin","kind":"pathway","name":"SWI/SNF chromatin remodelling","route":"/pathways/swi-snf-chromatin/"}],"term":[{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","route":"/terms/hereditary-cancer-syndromes/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"}],"paper":[{"id":"paper-acns0333-atrt-high-dose-chemotherapy-reddy-jco-2020","kind":"paper","name":"ACNS0333: high-dose chemotherapy and three-dimensional conformal radiation for atypical teratoid/rhabdoid tumour","route":"/key-papers/paper-acns0333-atrt-high-dose-chemotherapy-reddy-jco-2020/"},{"id":"paper-fruhwald-neuro-oncol","kind":"paper","name":"Age and DNA methylation subgroup as potential independent risk factors for treatment stratification in children with atypical teratoid/rhabdoid tumors","route":"/key-papers/paper-fruhwald-neuro-oncol/"}],"trial":[{"id":"acns0333","kind":"trial","name":"ACNS0333","route":"/trials/acns0333/"},{"id":"pediatric-match","kind":"trial","name":"NCI-COG Pediatric MATCH (APEC1621)","route":"/trials/pediatric-match/"}],"journal":[{"id":"brain-tumor-pathology","kind":"journal","name":"Brain tumor pathology","route":"/journals/brain-tumor-pathology/"},{"id":"cns-oncology","kind":"journal","name":"CNS oncology","route":"/journals/cns-oncology/"},{"id":"journal-of-neuro-oncology","kind":"journal","name":"Journal of neuro-oncology","route":"/journals/journal-of-neuro-oncology/"}]}}