DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for atypical teratoid rhabdoid tumor — screening already-approved drugs against its 18-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAtypical teratoid rhabdoid tumor maps to a 18-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for atypical teratoid rhabdoid tumor is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
MDM4 regulator of p53 (MDM4) — MDM4 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 3~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6Q9Y · 1.2 Å · ligand 7-methoxy-~{N}-[(3~{S})-1-(4-methylphenyl)pyrrolidin-3-yl]-1~{H}-indole-3-carboxamide (HRQ). Experimental structure, not a prediction.
What the evidence adds up to
Atypical teratoid rhabdoid tumour (AT/RT) is a rare, aggressive embryonal central nervous system tumour of infancy and early childhood. Prognosis is dismal despite aggressive multimodal treatment, with median survival historically estimated at 6 months to a year. A 2015 study of 16 patients treated with proton beam therapy (median age 18.5 months, range 5 months to 39 years) reported a median survival follow-up of 38.2 months and a mean overall survival estimate of 67.2 months (95% CI 44.4–81.6 months). Eight patients had metastatic disease at diagnosis; 11 showed no evidence of disease or stable disease, 3 were deceased, and 2 had disease progression. The treatment was described as well tolerated, with nausea, vomiting, skin erythema, weight loss, and fatigue as noted toxicities. A 2020 case report describes a 24-year-old male with left parietal AT/RT who remained recurrence-free 4 years after total resection, adjuvant chemotherapy, and radiotherapy.
A 2019 study of 20 patients used in vivo MR spectroscopy to identify metabolic subgroups. Tumours expressing achaete-scute homolog 1 (ASCL1) had higher creatine concentrations (3.42 ± 1.1 vs 1.8 ± 0.8 IU, P < .01) and higher myo-inositol (9.0 ± 1.5 vs 4.7 ± 3.6 IU, P < .05) compared with ASCL1-negative tumours, while lipid levels approached significance (44 ± 20 vs 80 ± 30 IU, P = .07). Brain-specific creatine kinase levels were higher in the ASCL1-positive cohort and correlated positively with absolute creatine and myo-inositol concentrations. The authors suggest MR spectroscopy might predict molecular features at diagnosis and aid risk stratification.
A 2024 Italian single-centre report describes three patients with INI1-negative AT/RT treated with tazemetostat as maintenance therapy in the relapse setting. Median age at diagnosis was 8 months (range 3–34 months). Patient 1 died of disease progression after 24 months, with an event-free survival of 9 months on tazemetostat. Patient 2 achieved a complete response and treatment was ongoing at 6 months. Patient 3 ended treatment after 12 months with a complete response. Median time on tazemetostat was 9 months (range 6–12 months). The authors note the drug was well tolerated but caution that only three patients were treated. A 2017 cytologic case report of a 4-year-old boy highlights that rhabdoid cells on touch imprint can be diagnostic if the pathologist is experienced, but that these cells were initially overlooked.
What is still missing: larger prospective trials for tazemetostat, validated metabolic stratification that can guide therapy, and any randomised comparison of proton beam therapy against photon radiotherapy or chemotherapy alone. The small numbers in every study — 16, 20, 3, or single cases — mean that no reliable survival estimate or treatment standard can be drawn from these data alone.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Neuroradiology · 2019 · 13 citations · open access
Pediatric Atypical Teratoid/Rhabdoid Tumors of the Brain: Identification of Metabolic Subgroups Using In Vivo <sup>1</sup>H-MR Spectroscopy
Abstract<h3>BACKGROUND AND PURPOSE:</h3> Atypical teratoid/rhabdoid tumors are rare, aggressive central nervous system tumors that are predominantly encountered in very young children. Our aim was to determine whether in vivo metabolic profiles correlate with molecular features of central nervous system pediatric atypical teratoid/rhabdoid tumors. <h3>MATERIALS AND METHODS:</h3> Twenty confirmed patients with atypical teratoid/rhabdoid tumors who underwent MR spectroscopy were included in this study. In vivo metabolite levels of atypical teratoid/rhabdoid tumors were compared with molecular subtypes assessed by achaete-scute homolog 1 expression. Additionally, brain-specific creatine kinase levels were determined in tissue samples. <h3>RESULTS:</h3> In vivo creatine concentrations were higher in tumors that demonstrated achaete-scute homolog 1 expression compared with those without achaete-scute homolog 1 expression (3.42 ± 1.1 versus 1.8 ± 0.8 IU, <i>P</i> < .01). Additionally, levels of myo-inositol (mI) (9.0 ± 1.5 versus 4.7 ± 3.6 IU, <i>P</i> < .05) were significantly different, whereas lipids approached significance (44 ± 20 versus 80 ± 30 IU, <i>P</i> = .07) in these 2 cohorts. Higher brain-specific creatine kinase levels were observed in the cohort with achaete-scute homolog 1 expression (<i>P</i> < .05). Pearson correlation analysis showed a significant positive correlation of brain-specific creatine kinase with absolute creatine (<i>P</i> < .05) and myo-inositol (<i>P</i> < .05) concentrations. <h3>CONCLUSIONS:</h3> In vivo MR spectroscopy may predict key molecular features of atypical teratoid/rhabdoid tumors at initial diagnosis, leading to timely patient risk stratification and accelerating the development of targeted therapies.
Journal of Cancer Research and Therapeutics · 2020 · 5 citations · open access
Brain atypical teratoid rhabdoid tumor in an adult with long-term survival: Case report and review of literature
AbstractAtypical teratoid/rhabdoid tumor (AT/RT) represents a rare malignant embryonic tumor of infant and early childhood. Its prognosis remains dismal despite aggressive multimodal treatment. We report the case of a 24-year-old male who was diagnosed with left parietal AT/RT after total resection and who is still in good health and recurrence free 4 years after surgery and adjuvant chemotherapy and radiotherapy.
International Journal of Particle Therapy · 2015 · 3 citations · open access
Single Center Results following Proton Beam Therapy in Children with Atypical Teratoid Rhabdoid Tumors of the Central Nervous System
AbstractPurpose Atypical teratoid rhabdoid tumor is a rare, embryonal, central nervous system tumor seen predominantly in infancy and childhood. Outcomes are generally dismal, with median survival estimated at 6 months to a year. The purpose of this study was to evaluate proton beam therapy (PBT) outcomes in this population. Materials and Methods Sixteen patients with a diagnosis of atypical teratoid rhabdoid tumor were treated from November 2007 to January 2013 at the Indiana University Health Proton Therapy Center. All patients were treated with PBT. Fraction sizes of 1.8 Gy/fraction were used to deliver 28 to 33 fractions. Seven patients received craniospinal PBT. There were 12 male and 4 female patients. The median age at diagnosis was 18.5 months (range, 5 months to 39 years). Eight had metastatic disease at diagnosis. Fourteen patients underwent surgery. Fifteen patients received chemotherapy. Results Median survival follow-up time was 3.18 years (or 38.2 months). The mean overall survival was estimated at 5.6 years (or 67.2 months; 95% confidence interval, 4.4–6.8 years). Patients of a median age of 18.5 months (range, 5.0–468 months) received a median radiation dose to the tumor bed of 54 Gy (range, 48.6–59.4 Gy). Eight patients also received craniospinal irradiation with a median dose of 36 Gy. Eleven patients showed no evidence of disease or stable disease, 3 patients were deceased, and 2 patients developed disease progression . Four patients suffered nausea and vomiting (common toxicity criteria [CTC] grade 2) as a result of treatment, and 4 patients also suffered moderate skin erythema (CTC grade 2). Two patients suffered from both weight loss and general fatigue during treatment. Conclusions The PBT was well tolerated in this heavily treated population. In the background of poor survival, these early outcome data are promising. Additional follow-up is necessary.
Journal of Education and Health Promotion · 2017 · 2 citations · open access
Cytologic diagnosis of atypical teratoid rhabdoid tumor based on touch imprint study: Report of a case with review of literature
AbstractAtypical teratoid rhabdoid tumor (ATRT) is a rare malignant tumor with gloom destiny. Our case was a 4-year-old boy with a temporal lobe tumor that was then became evident of ATRT with recurrent happening. In a retrospective review of all cytologic slides, we found unique rhabdoid cells that are morphologically evident cells for ATRT in both times. Unfortunately, the cells were overlooked at the first time. We conclude if the pathologist is experienced to see rhabdoid cells noticing these cells is highly helpful for diagnosis ATRT, especially in frozen sectioning.
ATRT-06. PEDIATRIC INI1-NEGATIVE ATYPICAL TERATOID RHABDOID TUMORS TREATED WITH TAZEMETOSTAT AS MAINTENANCE THERAPY IN THE RELAPSE SETTING: AN ITALIAN SINGLE-CENTRE EXPERIENCE
AbstractAbstract BACKGROUND Rhabdoid tumors are aggressive malignancies, primarily affecting children ≤3 years. Common sites of primary localization are kidney, central nervous system (atypical teratoid rhabdoid tumor -AT/RT-) or soft tissues. Although high-dose chemotherapy (HD-CT) with radiotherapy (RT) has significantly increased EFS and OS rates, more than 50% of patients diagnosed with AT/RT still die of tumor progression. METHODS From February 2021 to January 2024 three patients with AT/RT were treated with tazemetostat after first-line treatment (complete resection, CT, RT). RESULTS At diagnosis, patient 1 presented with a lesion in the lamina quadrigemina and a renal mass; patient 2 and 3 with a lesion in the posterior cranial fossa. Median age at diagnosis was 8 months (3-34 months). Patient 1 died due to the progression of the disease (OS 24 months); patient 2 ended treatment with tazemetostat on December 2023; for patient 3 the treatment is still ongoing. Patient 1 started tazemetostat at the end of first-line treatment, as maintenance therapy. Before starting treatment with tazemetostat, patient 2 performed a re-irradiation on the tumor bed; patient 3 performed surgery and then RT on a new-onset spinal lesion. Median time of treatment with tazemetostat was 9 months (6-12 months). Patient 1 showed an EFS of 9 months. EFS of patients 2 and 3 has exceeded this timepoint. For patient 2 the treatment is ongoing (in total 6 months of treatment), with a complete response of the disease (CR); patient 3 ended treatment after 12 months, with a CR. Tazemetostat was overall well tolerated. CONCLUSIONS Despite the small number of patients, we feel able to state that the use of tazemetostat as a single agent in the relapse setting could represent a therapeutic promise as maintenance therapy. Future studies with a larger number of patients are needed to confirm this hypothesis.
Turkish Journal of Oncology · 2014 · 0 citations · open access
Atipical teratoid rhabdoid tumor: case report and review of the literature
AbstractAtipical teratoid rhabdoid tumor (ATRT) is a rare and highly agressive malign tumor in the early childhood. Mean survival has been reported as 6-11 months. Despite the optimal treatment is unclear surgery, chemotherapy and radiotherapy are the well known treatment options. We would like to report a 4 year old boy who had the diagnosis of ATRT at the temporooccipital region to make a contribution to the literature.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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