DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Teratoma with Malignant Transformation — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTeratoma with Malignant Transformation maps to a 5-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 teratoma with malignant transformation 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
NRAS proto-oncogene, GTPase (NRAS) — NRAS 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZIO · 1.55 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
A 2009 review of teratomas in infants and children states that definitive therapy is complete surgical resection, and that early diagnosis, timely intervention and meticulous follow-up are critical for favourable long-term outcome. The review notes that teratomas are rare neoplasms composed of tissue elements derived from the germinal layers, most commonly found in sacrococcygeal, gonadal, mediastinal, retroperitoneal, cervicofacial and intracranial locations. Emerging evidence at that time indicated that age of diagnosis is an increasingly important prognostic feature independent of tumour location.
A 2015 international collaboration examined 320 patients with teratoma with malignant transformation diagnosed between 1981 and 2014. The tumour primary site was gonadal in 287 patients (89.7%), retroperitoneal in 17 (5.3%) and mediastinal in 16 (5%). Teratoma with malignant transformation and germ cell tumour were diagnosed concurrently in 130 patients (40.6%). Five-year overall survival was 83.4% (95% CI 61.3 to 93.5) in patients with clinical stage I, and worse than expected in those with metastasis. On multivariable analysis, nonprimitive neuroectodermal tumour histology, gonadal primary tumour and fewer prior chemotherapy regimens were independent predictors of better overall survival. Chemotherapy was not independently prognostic. The authors concluded that teratoma with malignant transformation generally had a worse prognosis than germ cell tumour, and that uncertainties persist regarding optimal chemotherapy.
A 2018 case report describes a 14-year-old boy with a mediastinal malignant teratoma who received surgical resection and pre- and postoperative chemotherapy. Three months after resection he developed pain in his right hip joint; systematic evaluation revealed multiple metastases, and a bone biopsy showed malignant melanoma arising from the malignant teratoma. The disease progressed rapidly, and he died 15 months after the original diagnosis. The authors note that this is the second reported case of malignant melanoma arising from a mediastinal malignant teratoma, and that both cases had a poor prognosis. They state that diagnosing and treating malignant transformation of teratoma, including malignant melanoma, is difficult because it is very rare.
What is still missing is a prospective trial design that can determine which chemotherapy, if any, improves survival for teratoma with malignant transformation, given that the 2015 collaboration found chemotherapy was not independently prognostic. Patient stratification by histology (nonprimitive neuroectodermal tumour versus other types) and primary site may be necessary, but the rarity of the condition makes accrual difficult. Adequate funding for multi-centre registries and randomised trials is lacking.
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 Pediatrics · 2009 · 146 citations
Teratomas in infants and children
AbstractPURPOSE OF REVIEW: Teratomas are rare neoplasms composed of tissue elements derived from the germinal layers of the embryo. Although they may originate anywhere along the midline, teratomas are most commonly found in sacrococcygeal, gonadal, mediastinal, retroperitoneal, cervicofacial and intracranial locations. Clinical behavior varies significantly by site and size. The presence of immature or premalignant elements may influence therapy and long-term outcome. This report reviews the current literature with regard to the diagnosis, management and outcome of teratomas in infants and children. RECENT FINDINGS: Recently, large case series have further elucidated the biologic behavior and clinical course of these rare tumors. Emerging evidence indicates that age of diagnosis is an increasingly important prognostic feature independent of tumor location. Advances in imaging are facilitating earlier diagnosis and identification of patients at higher risk of adverse outcome. In select cases, fetal and early neonatal interventions are improving outcome and survival. SUMMARY: Presenting symptoms may vary widely based on location; however, independent of primary location, definitive therapy for teratomas is complete surgical resection. Early diagnosis, timely intervention and meticulous follow-up are critical in the long-term favorable outcome.
Treatment and Clinical Outcomes of Patients with Teratoma with Somatic-Type Malignant Transformation: An International Collaboration
AbstractPURPOSE: We assessed prognostic factors, treatments and outcomes in patients with teratoma with malignant transformation, a rare occurrence among germ cell tumors. MATERIALS AND METHODS: Data on patients diagnosed with teratoma with malignant transformation between June 1981 and August 2014 were collected across 5 referral centers. Chemotherapy was dichotomized as based on germ cell tumor or teratoma with malignant transformation. Cox analyses were done to evaluate prognostic factors of overall survival, the primary end point. Each factor was evaluated in a univariable model. Forward stepwise selection was used to construct an optimal model. RESULTS: Among 320 patients the tumor primary site was gonadal in 287 (89.7%), retroperitoneal in 17 (5.3%) and mediastinal in 16 (5%). Teratoma with malignant transformation and germ cell tumor were diagnosed concurrently in 130 patients (40.6%). A total of 49 patients (16.8%) initially presented with clinical stage I. The remaining patients were at good (123 or 42.3%), intermediate (42 or 14.4%) and poor (77 or 26.5%) risk for metastasis according to IGCCCG (International Germ Cell Cancer Collaborative Group). First line chemotherapy was given for germ cell tumor in 159 patients (49.7%), chemotherapy for teratoma with malignant transformation was performed in 14 (4.4%) and only surgery was done in 147 (45.9%). Median followup was 25.1 months (IQR 5.4-63.8). Five-year overall survival was 83.4% (95% CI 61.3 to 93.5) in patients with clinical stage I and it was also worse than expected in those with metastasis. On multivariable analyses nonprimitive neuroectodermal tumor histology (overall p = 0.004), gonadal primary tumor (p = 0.005) and fewer prior chemotherapy regimens (p <0.001) were independent predictors of better overall survival. Chemotherapy was not independently prognostic. CONCLUSIONS: Less heavily pretreated teratoma with malignant transformation with a gonadal primary tumor and nonprimitive neuroectodermal tumor histology appears to be associated with longer overall survival. Generally, teratoma with malignant transformation had a worse prognosis than germ cell tumor. Uncertainties persist regarding optimal chemotherapy.
Case Reports in Pediatrics · 2018 · 6 citations · open access
A Case of Malignant Melanoma Arising in Mediastinal Malignant Teratoma
AbstractWe report about a 14-year-old boy who presented with an anterior mediastinal mass that was diagnosed as malignant teratoma. Surgical resection was performed along with pre- and postoperative chemotherapy. Although elevated alpha-fetoprotein became negative, he experienced pain in his right hip joint 3 months after resection. Systematic evaluation revealed multiple locations of metastasis, and the pathological diagnosis based on bone biopsy was malignant melanoma originating from malignant teratoma, which rapidly progressed. He died 15 months after diagnosis of the original malignant teratoma. Diagnosing and treating malignant transformation of teratoma, including malignant melanoma, is difficult because it is very rare. To our knowledge, this is the second reported case of malignant melanoma arising from a mediastinum malignant teratoma, with both cases having a poor prognosis. In addition to the follow-up of tumor markers, systematic evaluation, including imaging, should be considered even after remission to monitor malignant transformation of teratoma. We expect to establish a successful therapy and improve mortality rate after more such cases are accumulated.
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.
