DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for chordoma — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleChordoma maps to a 46-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 chordoma 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
MDM2 proto-oncogene (MDM2) — MDM2 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 {6-[(6-chloro-3-{1-[(4-chlorophenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5J7F · 2.0 Å · ligand 4-({6-[(6-chloro-3-{1-[(4-chlorophenyl)methyl]-4-(4-fluorophenyl)-1H-imidazol-5-yl}-1H-indole-2-carbonyl)oxy]hexyl}amino)-4-oxobutanoic acid (6GG). Experimental structure, not a prediction.
What the evidence adds up to
Twenty-one patients treated over twenty years received radiation doses between 5,000 cGy and 6,600 cGy, with symptom remission lasting one to six years. The authors concluded that high-dose radiation combined with complete or subtotal surgery offered the best chance for prolonged survival. In a separate series of fifteen patients treated between 1956 and 1990, twelve received radiotherapy and surgery. Actuarial survival was 58% at five years and 35% at ten years, but ten-year symptomatic progression-free survival was only 25%, symptom-free survival 17%, and disease-free survival 8%. The authors stated that the natural history of the disease seemed only marginally affected by treatment and that new therapeutic options were strongly needed.
A retrospective analysis of eighteen patients diagnosed between 2006 and 2010 found a mean age of 46.72 years, with sacrum the commonest site. Most patients did well after surgery and radiotherapy; one local recurrence occurred, and one patient with the dedifferentiated variant died on follow-up. The authors concluded that chordomas are effectively treated with resection and postoperative radiotherapy, despite being locally aggressive. A 1981 case report and literature review described chordoma as a low-grade, tenacious, eventually lethal neoplasm for which little improvement in outcome had been reported. The reported sacral chordoma responded temporarily to chemotherapy, and the authors noted that hyperthermic chemotherapy was feasible but had not yet been reported.
No abstract provides a controlled trial, and no abstract reports a drug repurposed for chordoma. The 1981 case describes a temporary response to chemotherapy in a single patient, but no drug name is given. The 1992 series explicitly states that new therapeutic options are strongly needed because existing treatment only marginally affected the natural history. What is still missing is any randomised trial design, any patient stratification by molecular subtype, and any dedicated funding for systematic drug screening in this rare tumour.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Radiology · 1986 · 136 citations
Chordoma: role of radiation therapy.
AbstractThe treatment of 21 patients with a diagnosis of chordoma seen over a 20-year period is described. The 13 men and eight women (ratio 1.6:1) ranged in age from 7 to 82 years (average, 50 years). Eleven chordomas arose from the clivus; the others originated in the sacral region (three patients), thoracic spine (one), cervical spine (three), and lumbar spine (three). Primary treatment consisted of surgery, reserving radiation therapy for recurrence in the majority of patients. Radiation doses, delivered with megavoltage equipment, ranged between 5,000 cGy delivered over 5 weeks and 6,600 cGy over 6 1/2 weeks. Irradiation produced significant tumor control, with remission of symptoms from 1 to 6 years. The combination of high-dose radiation therapy and complete or subtotal surgical resection offers the best chance for prolonged survival in this group of patients.
Archives of Pathology & Laboratory Medicine · 2021 · 111 citations · open access
Chordoma
AbstractCONTEXT.—: Chordomas are uncommon malignant neoplasms with notochordal differentiation encountered by neuropathologists, bone/soft tissue pathologists, and general surgical pathologists. These lesions most commonly arise in the axial skeleton. Optimal therapy typically involves complete surgical resection, which is often technically difficult owing to the anatomic location, leading to a high rate of recurrence. Lesions have been generally resistant to radiation and chemotherapy; however, experimental studies involving targeted therapy and immunotherapy are currently underway. OBJECTIVE.—: To summarize the clinical and pathologic findings of the various types of chordoma (conventional chordoma, dedifferentiated chordoma, and poorly differentiated chordoma), the differential diagnosis, and recent advances in molecular pathogenesis and therapeutic modalities that are reliant on accurate diagnosis. DATA SOURCES.—: Literature review based on PubMed searches containing the term "chordoma" that address novel targeted and immunomodulatory therapeutic modalities; ongoing clinical trials involved in treating chordoma with novel therapeutic modalities identified through the Chordoma Foundation and ClinicalTrials.gov; and the authors' practice experience combined with various authoritative texts concerning the subject. CONCLUSIONS.—: Chordoma is a clinically and histologically unique malignant neoplasm, and numerous diagnostic considerations must be excluded to establish the correct diagnosis. Treatment options have largely been centered on surgical excision with marginal results; however, novel therapeutic options including targeted therapy and immunotherapy are promising means to improve prognosis.
Fifty Years of Experience with Chordomas in Southeast Scotland
AbstractWe report the clinical presentation and management of 34 patients with a histologically proven chordoma, treated in the neurosurgical departments in Edinburgh and Dundee, over the past 50 years. Although these tumors are commonly regarded as being locally invasive with a variable, but generally slow growth rate, they can metastasize, and this may precede surgical intervention, as in one of our patients. Our cases are compared to those in previously published series, and a comprehensive review of the treatment modalities for tumors at various sites is presented. The optimal treatment to be recommended from our own experience, and that of others, is aggressive operation and radiotherapy. A combination of hyperthermia and chemotherapy has shown some promise, but remains untested, and highlights the need for a multicenter trial with long follow-up to allow the evaluation of new therapeutic approaches.
Acta Oncologica · 1992 · 60 citations · open access
Chordoma-Natural History, Treatment and Prognosis the Florence Radiotherapy Department Experience (1956-1990) and a Critical Review of the Literature
AbstractFifteen cases of chordoma, seen between 1956 and 1990 at the Florence Radiotherapy Department are reported. Twelve of them were treated with radiotherapy and surgery, while one was left untreated. We analyzed the course of the disease in the treated cases, with particular emphasis on the problem of symptom control. The natural history of the disease seemed to be only marginally affected by the treatment and new therapeutic options are strongly needed. While actuarial survival rates at 5 and 10 years were 58% and 35% respectively (owing to the slow growth rate of this neoplasm), 10 years' symptomatic progression-free, symptom-free, and disease-free survival rates were only 25%, 17% and 8% respectively.
Turkish Neurosurgery · 2012 · 19 citations · open access
Clinicopathological characteristics of chordoma - an institutional experience and a review of literature
AbstractAIM: To study the clinicopathologic characteristics of chordomas from a single institution. MATERIAL AND METHODS: This study is a retrospective analysis of 18 cases of chordomas diagnosed over a period of 5-years at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, from 2006 to 2010. RESULTS: The overall mean age of the patients was 46.72 years. Males outnumbered females. Sacrum was the commonest site involved. Histopathologically, the majority of cases were conventional chordoma with four cases of chondroid variety. There was a single case of dedifferentiated chordoma that presented with bone metastasis. Most patients did well after surgery and radiotherapy. One patient had a local recurrence and one patient with dedifferentiated variant died on follow-up. CONCLUSION: Though locally aggressive, chordomas are effectively treated with resection and postoperative radiotherapy.
Journal of Surgical Oncology · 1981 · 16 citations
Sacral chordoma: A case study and review
AbstractChordomas are a low grade, tenacious, but eventually lethal neoplasm for which little improvement in outcome has been reported. A current review of the literature and a case report are provided to support his position. The reported sacral chordoma did respond temporarily to chemotherapy. Its rare occurrence precludes controlled studies of chordoma; therefore, any response merits reporting. The authors observed that hyperthermic chemotherapy was feasible for treating some chordomas but has not yet been reported. It was evaluated for the patient in this report.
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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