DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for bone giant cell tumor — 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 moduleBone giant cell tumor 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 bone giant cell 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
TNF superfamily member 11 (TNFSF11) — TNFSF11 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 5BNQ · 2.8 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Giant cell tumours account for about 5–8% of primary bone tumours. A 1988 case report of a metatarsal giant cell tumour treated with en bloc resection and bone graft reported an excellent result at four-year follow-up, but that single case cannot support general conclusions. A 2024 retrospective study from a single Indian institution compared radiotherapy alone (54 Gray in 27 fractions) with neoadjuvant denosumab (eight doses) followed by surgery in patients with histopathologically proven giant cell tumour of bone. Among 22 patients in the radiotherapy arm and 26 in the denosumab-plus-surgery arm, five-year locoregional failure-free survival was 81.8% and 76.9% respectively, a difference that was not statistically significant (P = 0.680). Quality of life, measured by the EQ-5D-5L questionnaire, also did not differ significantly between the two groups (P = 0.850). The authors concluded that both approaches produce similar locoregional control and quality of life in patients with initially unresectable tumours.
A 2021 Russian study of 277 patients treated between 2005 and 2020 compared surgery alone (n = 212) with neoadjuvant denosumab followed by surgery (n = 65). Denosumab was given subcutaneously at 120 mg on days 1, 8, 15, and 28, then every four weeks until a stable effect was achieved. In patients who underwent radical surgery, the local recurrence rate was 12% in the surgery-alone group and 0% in the combination group; this difference was significant (P < 0.05). The combination group also had significantly milder pain during treatment, and among those with challenging anatomical tumour locations, neoadjuvant denosumab substantially reduced both duration of surgery and blood loss (P < 0.05). The incidence of complications after radical surgery was 36.9% in the surgery-alone group and 12.5% in the combination group (P < 0.05). However, tumour location and the volume of surgery remained important determinants of recurrence.
The 2024 study is limited by its small sample size, retrospective design, and single-institution setting. The 2021 study, though larger, is also retrospective and from a single centre. Neither trial was randomised, and both lack long-term safety data for denosumab in this context. What is still missing is a prospective, randomised trial with sufficient power to detect differences in recurrence and survival, standardised patient stratification by tumour location and surgical grade, and independent funding that does not rely on the drug manufacturer.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Foot & Ankle · 1988 · 19 citations
Giant Cell Tumor of the Metatarsal
AbstractThe following is a report of a giant cell tumor of a metatarsal, description of treatment, and review of the literature. Giant cell tumors comprise approximately 5-8% of the primary bone tumors. Metatarsal bones are a very rare primary site of involvement. Clinically aggressive or benign behavior cannot be predicted histologically. Treatment should be aggressive, as in this case where en bloc resection and bone graft were performed. Results were excellent with 4 yr follow-up.
Cancer Research Statistics and Treatment · 2024 · 4 citations · open access
Comparison between radiotherapy and neoadjuvant denosumab followed by surgery in the treatment of giant cell tumor of bone: A retrospective observational study
AbstractABSTRACT Background: Giant cell tumor is a locally aggressive tumor of the bone. In the predenosumab era, treatment comprised surgery or radiotherapy in potentially resectable lesions. After the advent of denosumab, utilizing neoadjuvant denosumab followed by surgery has emerged as an effective treatment option. Objectives: We aimed primarily to assess and compare the locoregional failure-free survival of patients with giant cell tumor of the bone (GCTB) treated with either external beam radiotherapy or neoadjuvant denosumab followed by surgery. The secondary objective was to assess and compare the quality of life (QoL) of patients between the two arms. Materials and Methods: In this single institutional retrospective study, conducted between August 2022 and August 2023 in the Department of Radiotherapy in the Institute of Post Graduate Medical Education and Research and SSKM Hospital Kolkata, West Bengal, India, we included patients with histopathologically proven GCTB. These patients were treated with either radiotherapy (54 Gray in 27 fractions) or neoadjuvant denosumab (for 8 doses) followed by surgery and were followed up at least for 6 months after completing the first-line therapy. Patients were monitored every 3 months for 2 years and then every 6 months thereafter. Locoregional control of the tumor was assessed by clinical examination and imaging. QoL was assessed and compared by the EQ-5D-5L questionnaire and health today scoring system. Results: We enrolled 22 patients in the radiotherapy alone group and 26 patients in the group receiving neoadjuvant denosumab followed by surgery. The 5-year locoregional failure-free survival was achieved in 18/22 patients (81.8%) in the radiotherapy arm and in 20/26 patients (76.9%) in the neoadjuvant denosumab group (P, 0.680). There was no significant difference in the QoL between the two groups of patients (P, 0.850). Conclusion: Radiotherapy and neoadjuvant denosumab followed by surgery result in similar locoregional control and quality of life in the patients with giant cell tumor of bones, and both can be considered appropriate treatment options in patients with initially unresectable tumors.
Bone and soft tissue sarcomas tumors of the skin · 2021 · 3 citations · open access
Results of neoadjuvant denosumab in giant cell tumor of the bone depending of the tumor location and the surgical grade
AbstractBackground. The standard treatment for giant-cell tumors of the bone includes radical surgery. However, specific anatomical location of the tumor and/or its spread may hinder its complete excision or result in poor functional outcomes. Currently, combination treatment that includes preoperative denosumab and surgery is preferable. It saves patients’ lives and improves their quality of life. Reduction of local recurrence rate by combination therapy for giant-cell tumors of the bone is being actively studied now.Objective – to analyze treatment outcomes of patients with giant-cell tumors of the bone, including those who received combination treatment that included preoperative therapy with denosumab followed by surgery.Materials and methods. This study included 277 patients with giant-cell tumors treated in N.N. Blokhin National Cancer Research Center between 2005 and 2020. The mean duration of follow-up was 56 months. Study participants were divided into two groups. Group 1 included patients who received surgical treatment alone (n = 212), whereas Group 2 comprised patients who received combination treatment (n = 65). Neoadjuvant therapy included subcutaneous denosumab 120 mg on days 1, 8, 15, and 28, then every 4 weeks until stable effect. There were two variants of surgical treatment: radical (removal by a single block or segmental resection with defect replacement, with or without fixation) and non-radical (excochleation or marginal resection with defect replacement, with or without fixation).Results. During treatment, patients in Group 2 had a significantly milder pain syndrome (assessed both using the visual analog scale for pain and Watkins scale) compared to Group 1. In case of radical surgery, the incidence of local recurrence was 12 % and 0 % in Groups 1 and 2, respectively; the difference was significant (р 0.05). Tumor location and volume of surgery played an important role in disease recurrence (р 0.05). The incidence of complications after radical surgery was 36.9 % and 12.5 % in Groups 1 and 2, respectively; the difference was significant (р 0.05). In addition to that, neoadjuvant therapy with denosumab substantially reduced the duration of surgery and blood loss in patients with challenging anatomical location of the tumor (р 0.05).Conclusion. Combination treatment for giant-cell tumors that includes neoadjuvant therapy with denosumab reduces the risk of recurrence, duration of surgery, blood loss, and the risk of postoperative complications. However, it is important to consider tumor location and the volume of surgery. Since the disease is quite rare, further study of long-term efficacy and safety of combination treatment for giant-cell tumors, including rare ones and those with challenging anatomical location, is necessary.
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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