DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for cerebellar pilocytic astrocytoma — screening already-approved drugs against its 22-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCerebellar pilocytic astrocytoma maps to a 22-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 cerebellar pilocytic astrocytoma 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
isocitrate dehydrogenase (NADP(+)) 1 (IDH1) — IDH1 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 ictdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6BKX · 1.65 Å · ligand ISOCITRIC ACID (ICT). Experimental structure, not a prediction.
What the evidence adds up to
In a series of 132 patients operated for cerebellar astrocytoma between 1960 and 1984, 105 had pilocytic histology. Their 5-year, 10-year, and 20-year survival rates were 85%, 81%, and 79%, respectively. Multivariate analysis showed that the division between pilocytic and diffuse histologic type was the most significant prognostic factor for survival. Pilocytic tumours occurred in younger patients and were more often cystic and completely resected.
A separate study of 112 children aged 3 months to 3 years operated for cerebellar astrocytoma between 1980 and 2019 reported postoperative mortality of 15.2% over 30 years. Among those with diffuse differentiated (low-grade) astrocytoma, average follow-up was 6.7 years, good quality of life was noted in 39.4%, and 7.3% died in the long term. For poorly differentiated (high-grade) diffuse astrocytoma, average follow-up was 4.3 years, satisfactory quality of life was seen in 68.0%, poor quality in 22.0%, vegetative state in 10.0%, and 20.0% died. The authors concluded that degree of differentiation and radicality of removal correlated with quality and length of life.
Long-term functional outcome was assessed in 18 adolescents and 46 adults treated for low-grade cerebellar astrocytoma in childhood. Mean time from surgery was 7.8 years for adolescents and 12.9 years for adults. Five adults (11%) had major sequelae related to postoperative complications, mutism, or brain stem involvement. The remaining participants had close-to-normal academic achievement and normal autonomy despite a high rate of reported cognitive difficulties and mild neurological sequelae such as fine motor problems and balance issues. The authors judged long-term functional outcome generally favourable in the absence of postoperative complications and brain stem involvement.
A comparison of intraoperative MRI (iMRI) versus no iMRI in 60 sequential patients with hemispheric cerebellar pilocytic astrocytoma found no significant difference in repeat surgery within 30 days (9% without iMRI, 0% with iMRI), residual disease at 3 months (19% vs 14%), or second resection beyond 30 days (9% vs 4%). Operative time was shorter without iMRI (4.4 vs 6.1 hours). Total reoperations were 19% without iMRI and 4% with iMRI, but this difference did not reach statistical significance. The authors concluded that iMRI tended to leave less residual and fewer reoperations, but neither outcome achieved significance, leaving utilisation to surgeon discretion. What remains missing are prospective trials large enough to detect whether iMRI reduces reoperation rates, studies that stratify patients by tumour location and cystic versus solid composition, and funding for long-term cognitive and quality-of-life follow-up beyond single-institution retrospective series.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 1993 · 132 citations · open access
Astrocytomas of the cerebellum: A comparative clinicopathologic study of pilocytic and diffuse astrocytomas
AbstractBACKGROUND: The majority of patients with astrocytomas of the cerebellum have an excellent prognosis; however, a small percentage of patients continue to do poorly. To clarify the clinical, pathologic, and treatment characteristics that determine prognosis and therapeutic recommendations, a large group of patients with astrocytic tumors of the cerebellum was reviewed and analyzed. METHODS: A clinicopathologic analysis was performed of all patients undergoing initial operation for astrocytomas in the cerebellum between 1960 and 1984. Of the 132 patients, 105 patients had pilocytic astrocytomas and 27 had diffuse astrocytomas. RESULTS: Multivariate analysis revealed that the division of pilocytic and diffuse histologic type was the most significant prognostic factor influencing survival. The 5-year, 10-year, and 20-year survival rates were 85%, 81%, and 79%, respectively, for patients with pilocytic astrocytomas and 7%, 7%, and 7%, respectively, for patients with diffuse astrocytomas (P < 0.001). Pilocytic astrocytomas occurred in a younger age group and were more commonly cystic and completely resected. CONCLUSIONS: Astrocytomas of the cerebellum can be divided into two principal groups, the pilocytic and the diffuse astrocytomas, each of which has distinct clinical, pathologic, and prognostic characteristics.
Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood
AbstractUNLABELLED: Abstract Purpose: A number of studies report neurological and cognitive deficits and behavioural disorders in children after surgical treatment for a benign cerebellar tumour. The present study explores functional outcome in adolescents and adults treated for a low-grade cerebellar astrocytoma in childhood. MATERIALS AND METHODS: Participants were 18 adolescents and 46 adults treated for low-grade astrocytoma in childhood. Academic achievement, professional status and neurological, cognitive and behavioural disturbances were collected using self-completed and parental questionnaires for adolescents and phone interview for adults. For the adolescent group, a control group filled in the same questionnaires. RESULTS: Mean time lapse from surgery was 7.8 years for adolescents and 12.9 years for adults. Five adults (11%) had major sequelae related to post-operative complications, post-operative mutism and/or brain stem involvement. All the other participants presented close-to-normal academic achievement and normal autonomy, despite a high rate of reported cognitive difficulties and difficulties related to mild neurological sequelae (fine motor skills, balance). CONCLUSION: The long-term functional outcome of low-grade cerebellar astrocytoma is generally favourable, in the absence of post-operative complications and brain stem involvement. No major impact of neurological deficits, cognitive problems and emotional disorders on academic achievement and independent functioning was observed.
The Utility of Intraoperative Magnetic Resonance Imaging in the Resection of Cerebellar Hemispheric Pilocytic Astrocytomas: A Cohort Study
AbstractBACKGROUND: The mainstay of treatment for cerebellar pilocytic astrocytomas in the pediatric population is surgery. The use of intraoperative magnetic resonance imaging (iMRI) as a surgical adjunct may lower the likelihood of reoperation. Studies have examined iMRI in heterogenous tumor populations, but few have looked at single pathologies. OBJECTIVE: To compare iMRI vs non-iMRI for hemispheric cerebellar pilocystic astrocytomas, specifically looking at revision surgeries and residual disease in follow-up. METHODS: Retrospective review of medical records for 60 sequential patients with cerebellar hemispheric pilocytic astrocytoma at a single institution was conducted. Thirty-two patients with cerebellar pilocytic astrocytoma underwent surgery without iMRI, whereas 28 patients underwent surgical resection with iMRI. All patients had at least 3-year follow-up. RESULTS: There were no significant differences between the patient populations in age, tumor size, or need for cerebrospinal fluid diversion between groups. Operative time was shorter without iMRI (without iMRI 4.4 ± 1.3 hours, iMRI 6.1 ± 1.5, P = .0001). There was no significant difference in the patients who had repeat surgery within 30 days (9% without iMRI, 0% iMRI, P = .25), residual disease at 3 months (19% without iMRI, 14% iMRI, P = .78), or underwent a second resection beyond 30 days (9% without iMRI, 4% iMRI, P = .61). There were more total reoperations in the group without iMRI, although this did not reach significance (19% vs 4%, P = .11). CONCLUSION: For hemispheric cerebellar pilocytic astrocytomas, iMRI tended to leave less residual and fewer reoperations; however, neither of these outcomes achieved statistical significance leaving utilization to be determined by the surgeon.
Features of surgical treatment of cerebellar astrocytomas in children of the first years of life
AbstractIntroduction: Astrocytomas make up to 30-50% of all brain tumors in children and remains one of the actual problems of pediatric neurosurgery.Objective: To conduct a retrospective analysis of the treatment of cerebellar astrocytomas in children of early age during 30 years, to identify the factors determining the prognosis of the disease.Materials and methods: Results of treatment of 83 children of early age, operated for astrocytomas of cerebellum in the Pediatric Department in 1980-2009 years were analyzed. Male patients were 48 (57.8%), female — 35 (41.2%). Benign astrocytomas are diagnosed in 67 (80.7%) cases and malignant in 16 (19.3%). Astrocytoma of the cerebellum in 43 (51.8%) children contained a cystic component. Postoperative mortality over a 30-year period was 15.8%. Catamnesis was analyzed in 65 patients in terms in average 6.1 years. The evaluation of quality of life was based on a scale Yu.A. Orlov (2007).Results: The total removing of the tumor was done in 61.9% of patients, subtotal in 26.3%, partial in 11.8%, biopsies of tumours in 1.2%. Shunt surgery complement the removing of tumors in 40.8% cases. Postoperative mortality rate decreased from 18.2% in 1980-1989. to 6.7% in 2000-2009. In 1980-1989 years total removal was in 35.4%, in 2000-2009 in 66.7%. Survival at 1 year after operation was in 93.8%, 2 years – in 86.1%, 5 years – in 67.7% of cases. The good quality of life was noted in 21 (32.3%) of the children, satisfactory in 35 (53.8%), poor in 7 (10.8%) and the vegetative state in 2 (3.1%) children.Conclusions: The amount of removal of the tumor, the degree of malignancy, presence of cystic components affect the quality and duration of life of children of early age with cerebellar astrocytomas.
Ukrainian Interventional Neuroradiology and Surgery · 2021 · 0 citations · open access
Results of surgical treatment of cerebellar astrocytomas in young children
AbstractObjective ‒ to analyze the results of surgical treatment of cerebellar astrocytomas in young children, to establish the factors that determine the prognosis of the course of the disease.Materials and methods. The results of surgical treatment of 112 children with cerebellar astrocytoma, who were operated in Romodanov Neurosurgery Institute of NAMS of Ukraine in 1980‒2019; 59.8 % were boys, 40.2 % were girls. The age of children ‒ from 3 months to 3 years. Removal of the tumor was performed in 106 patients: in 58 ‒ totally, in 31 ‒ subtotally, in 16 ‒ partially, in 1 ‒ biopsy. Diffuse differentiated astrocytoma (low-grade (II)) was detected in 94 (83.9 %) patients, poorly differentiated diffuse astrocytoma (high-grade (III)) ‒ in 18 (16.1 %). In the cerebellum astrocytomas in 77 (68.7 %) cases were located in the midline. In 59 (52.7 %) cases astrocytomas had a cystic component, in 53 (47.3 %) cases were solid ones. Postoperative mortality over 30 years of observations was 15.2 %. Results. It was found that survival rates in the early postoperative period were statistically (p = 0.03) better in cases of total tumor resection compared with patients after with subtotal resection. In patients with diffuse differentiated astrocytoma of the cerebellum, the average duration of follow-up was 6.7 years, a good quality of life was noted in 39.4 % of patients. In the long-term follow-up period, 7.3 % of children died. In patients with poorly differentiated diffuse astrocytoma of the cerebellum, the average duration of follow-up was 4.3 years, while a satisfactory quality of life was observed in 68.0 % of patients, a poor quality in 22.0 %, and a vegetative state in 10.0 % of children. In the long-term period, 20.0 % of children died. Microscopic features of cerebellar astrocytomas are their expansive-infiltrative nature of distribution and the presence of zones of neoangiomatosis.Conclusions. It was revealed that the degree of differentiation of diffuse cerebellar astrocytomas and the radicality of their removal correlates with the quality and life expectancy of patients. The tendency of the influence of the degree of malignancy of astrocytomas on the indicators of general and reccurence-free survival of children of the younger age group was noted.
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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