DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for infant-type hemispheric glioma — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleInfant-type hemispheric glioma maps to a 1-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 infant-type hemispheric glioma 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
BRCA1 DNA repair associated (BRCA1) — BRCA1 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8RS8 · 1.31 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Infant-type hemispheric glioma is diagnosed in patients less than 12 months old. A 2024 case series from Hong Kong identified eight such patients, mean age 3 months, seven with glioblastoma and one with anaplastic astrocytoma. Four had multilobar involvement. NTRK fusions were found in four patients (ETV6-NTRK3 and TPR-NTRK1), ALK fusion in one (HMBOX1-ALK), and ROS1 fusion in one (ZCCHZ8-ROS1). All eight received chemotherapy; four were switched to NTRK inhibitors and one to a ROS1 inhibitor. Surgery was performed at various time points. Two patients died, at 22 and 35 months of age. The abstract states that overall survival of infantile high-grade glioma is superior to other high-grade gliomas, but does not give a survival rate for the series.
A 2022 case report describes a nine-month-old boy with infant-type hemispheric glioma (gliosarcoma subtype) in the left frontal lobe. After subtotal resection he received chemotherapy with the BABY POG protocol. Molecular analysis showed a TPR-NTRK1 fusion. He was then treated with the TRK inhibitor larotrectinib and exhibited stable disease with a residual lesion after 8 months of targeted therapy. This is the first reported infantile gliosarcoma with an NTRK1 rearrangement treated with larotrectinib.
A 1997 review notes that malignant gliomas in infants appear to be distinct entities from adult malignant gliomas. It states that pediatric low-grade gliomas and adult gliomas do not share similar molecular genetic features. The review does not address infant-type hemispheric glioma specifically and offers no survival data for this tumour type.
What is still missing is a prospective trial large enough to test whether targeted therapy improves survival over chemotherapy alone, given that the Hong Kong series reports only eight patients and the case report only one. The optimal timing of surgery relative to targeted agents is not established, and no randomised comparison of NTRK, ALK, or ROS1 inhibitors against standard chemotherapy exists for this age group. Patient stratification by fusion subtype and extent of resection remains unvalidated.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Oncology · 1997 · 4 citations
Advances and controversies in the management of childhood brain tumors
AbstractImportant studies have been reported in the past year on the biology and management of pediatric central nervous system tumors. Pediatric low-grade gliomas and adult gliomas do not share similar molecular genetic features. There may be a role for high-dose chemotherapy with bone marrow rescue in relapsed medulloblastoma and germinoma. Malignant gliomas in infants appear to be distinct entities compared with adult malignant gliomas. Further investigational studies are needed in ependymoma and diffuse pontine gliomas because current therapies have not resulted in improvements in outcomes.
Chinese Clinical Oncology · 2024 · 0 citations · open access
AB055. Infantile high-grade glioma (IHG)—a case series of Hong Kong experience
AbstractBACKGROUND: Infantile high-grade glioma (IHG) is diagnosed in patients less than 12 months of age. Studies have shown that it displays a more stable genome and is usually single mutation-driven. The most identifiable mutations are receptor tyrosine kinase (RTK) fusion, such as neurotrophic tyrosine receptor kinase (NTRK) family, reactive oxygen species (ROS1), anaplastic lymphoma kinase (ALK), and mesenchymal-epithelial transition (MET) factor. The current principal treatment remains to be surgery, but it is challenging for a complete resection due to hemispheric involvement. Use of chemotherapeutic drugs for IHG is still under debate, with targeted therapy showing efficacy in promoting tumor shrinkage. Despite being a challenging central nervous system (CNS) tumor, the overall survival of IHG is superior to other high-grade gliomas. CASE DESCRIPTION: This is a retrospective review of local IHG patients and their outcome. Up till the end of 2022, we identified eight IHG patients in our local data. Mean age of diagnosis was 3 months. There were four males and four females. Seven patients had histological diagnosis of glioblastoma and one patient had a diagnosis of anaplastic astrocytoma. One patient had her tumor located in the infratentorial region. Four patients had multilobar involvement. NTRK fusion was found in four patients (ETV6-NTRK3 fusion and TPR-NTRK1 fusion). ALK fusion was found in one patient (HMBOX1-ALK). ROS1 fusion was found in one patient (ZCCHZ8-ROS1). All patients underwent chemotherapy, with four patients switched to NTRK inhibitors and one patient to ROS1 inhibitors afterward. Surgery was performed at various time points for these patients. Two patients passed away, at 22 and 35 months of age at submission of this abstract. CONCLUSIONS: Infantile high-grade glioma should be regarded as a unique tumor entity and a multidisciplinary approach is paramount in improving survival for this group of patients.
Supplementary Material for: A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with <b><i>TPR</i></b>-<b><i>NTRK1</i></b> Fusion Treated with Larotrectinib
AbstractHerein, we present a rare case of a nine-month-old boy diagnosed with infant-type hemispheric glioma (gliosarcoma subtype) at the left frontal lobe. Following subtotal resection, the patient started chemotherapy with the BABY POG protocol. We describe the clinical diagnosis, histological characteristics, radiological features, molecular aspects, and management of this tumor. A comprehensive molecular analysis on the tumor tissue showed a <i>TPR-NTRK1</i> gene fusion. The patient was treated with a TRK inhibitor, larotrectinib, and exhibited a stable disease with residual lesion following 8 months of target therapy. The present study is the first report of an infantile gliosarcoma harboring <i>NTRK1</i> rearrangement treated with larotrectinib.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
