DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for osteosarcoma — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleOsteosarcoma maps to a 45-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
approvedDocetaxelApproved drugapprovedPaclitaxelApproved drug
Structures already discussed alongside osteosarcoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Refined structure of alpha-beta tubulin from zinc-induced sheets stabilized — Paclitaxel has a real, experimentally solved structure in complex with this target (PDB 1JFF, 3.5 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet ta1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1JFF · 3.5 Å · ligand Paclitaxel (TA1). Experimental structure, not a prediction.
What the evidence adds up to
In a retrospective Chinese study of 18 patients with recurrent or refractory high-grade osteosarcoma, gemcitabine-docetaxel combination therapy produced an overall response rate of 5.6% and a disease control rate of 22.3%. One partial response and three cases of stable disease were observed. Median time to progression was 2 months (range 2–6 months) and median overall survival was 8 months (range 3–21 months). Severe haematologic toxicities occurred in a notable proportion of cycles: grade 3 or 4 leucopenia in 29.5%, thrombocytopenia in 18.1%, and anaemia in 9.1%. No treatment-related deaths were reported. The authors described the regimen as marginally effective.
The Brazilian Osteosarcoma Treatment Group reported outcomes from three prospective cohorts enrolling 604 patients under 30 years of age with high-grade osteosarcoma. Among 553 eligible patients, estimated 5-year overall survival was 49% and event-free survival was 39%. For the 390 non-metastatic patients, 5-year overall survival was 59% and event-free survival was 48%. Metastases at diagnosis, primary tumour site, type of surgery, and histological response were significant predictors of survival. The authors noted that these survival rates are below those reported in current literature.
A 2024 laboratory study examined polyphyllin I combined with TRAIL in two human osteosarcoma cell lines, MG-63 and U-2 OS. The combination reduced cell viability, migration, and invasion, and increased apoptosis and cell cycle arrest compared to either agent alone. The effect was linked to inactivation of the Wnt/β-catenin signalling pathway. This work is limited to cell culture and does not provide clinical data on safety or efficacy in patients.
What remains missing is prospective trial evidence for gemcitabine-docetaxel in a larger, stratified patient population; funding to replicate or extend the Brazilian collaborative model with modern treatment protocols; and clinical translation of the polyphyllin I–TRAIL combination, which currently lacks any human data on dosing, toxicity, or tumour response.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Japanese Journal of Clinical Oncology · 2012 · 22 citations · open access
Efficacy and Safety of Gemcitabine-Docetaxel Combination Therapy for Recurrent or Refractory High-grade Osteosarcoma in China: A Retrospective Study of 18 Patients
AbstractOBJECTIVE: In this study, we describe experiences with gemcitabine-docetaxel combination therapy as salvage treatment for Chinese patients with recurrent or refractory high-grade osteosarcoma. METHODS: We retrospectively reviewed the medical records of 18 patients with recurrent or refractory high-grade osteosarcoma who had undergone gemcitabine-docetaxel combination treatment as salvage chemotherapy. Gemcitabine at 675 mg/m(2) was administered on Days 1 and 8, and docetaxel at 75-100 mg/m(2) was administered on Day 8. The combination therapy was repeated every 3 weeks. Treatment was continued until evidence of disease progression or unacceptable toxicity. RESULTS: The patients (ages 12-57 years) received a total of 44 cycles of chemotherapy (median: 2 courses; range: 2-6 courses). The overall response rate was 5.6% and the disease control rate was 22.3%, with one partial response and three patients with stable disease. The median time to progression and overall survival time were 2 months (range: 2-6 months) and 8 months (range: 3-21 months), respectively. Major severe toxicities were hematologic toxicities, including Grade 3 or 4 anemia (9.1%), leucopenia (29.5%) and thrombocytopenia (18.1%) in total cycles; mild toxicities included Grade 1 or 2 nausea and vomiting (31.8%), fatigue (38.6%) and alopecia (20.5%). There were no treatment-related deaths. CONCLUSIONS: In the current study, gemcitabine-docetaxel combination therapy at this dosage and schedule was found to be well tolerated and marginally effective, which could be considered as salvage therapy for patients with recurrent or refractory high-grade osteosarcoma.
Journal of Adolescent and Young Adult Oncology · 2013 · 16 citations · open access
Fifteen Years' Experience of the Brazilian Osteosarcoma Treatment Group (BOTG): A Contribution from an Emerging Country
AbstractPURPOSE: Little information is available regarding the tumor features, prognostic factors, and treatment results in children and adolescents and young adults (AYAs) with osteosarcoma diagnosed in developing countries. We reviewed the results of three observational cohorts of osteosarcoma patients treated in an emerging country. METHODS: A total of 604 patients below the age of 30 years with high-grade osteosarcoma were prospectively enrolled in the Brazilian Osteosarcoma Treatment Group (BOTG) studies III, IV, and V. Gender, age, time from onset of symptoms to diagnosis, primary tumor site, presence or absence of metastases at diagnosis, tumor size, type of surgery (limb-sparing or amputation), treatment protocol, and histological response were correlated with survival. RESULTS: The estimated 5-year overall survival and event-free survival (EFS) rates for the 553 eligible patients were 49% and 39% respectively; of the 390 non-metastatic patients included in the total, overall- and event-free survival were 59% and 48% respectively. Metastases at diagnosis, primary tumor site, type of surgery, and histological response were significant predictors of overall survival and EFS in univariate and multivariate analysis, whereas tumor size and treatment protocol lost prognostic significance in multivariate analysis. CONCLUSION: We report on the outcome of three consecutive studies for the treatment of osteosarcoma carried out in Brazil over 15 years. Although the survival rates presented are below those reported in current literature, it represents the result of a favorable experience gathered from the national collaborative work.
Asian Pacific Journal of Cancer Prevention · 2012 · 13 citations · open access
Induction of Apoptosis by a Combination of Paclitaxel and Carboplatin in the Presence of Hyperthermia
AbstractPURPOSE: To study enhancing effects of paclitaxel in the thermochemotherapy of osteosarcoma cell lines and related mechanisms. MATERIALS AND METHODS: Paclitaxel and carboplatin were used alone or jointly on OS732 cell lines in the presence of hyperthermia. Inhibition of proliferation was measured by MTT assay and cellular changes were assessed with inverted phase contrast and fluorescence microscopy. Apoptosis was analyzed with flow cytometry (FCM) and Fas expression by immunocytochemistry. RESULTS: At 43 degrees C, one hour after the application of 10 μg/ml paclitaxel and 5 μg/ml carboplatin on OS732 cells jointly, the survival rate was 15.8% which was significantly lower than with 10 μg/ml paclitaxel (45.8%) and 5 μg/ml carboplatin (47.7%) respectively (P<0.01). Moreover, changes of morphology and apoptotic rates indicated that the apoptosis-inducing effect of combined application was also much enhanced, as evident also regarding Fas expression. CONCLUSION: Paclitaxel is conducive to thermochemotherapy of osteosarcoma cell lines, possibly accomplished by up-regulation of Fas expression with induction of apoptosis.
Polyphyllin I enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth downregulating the Wnt/β-catenin pathway.
AbstractOBJECTIVE: To investigate the synergistic effects of polyphyllin I (PPI) combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway. METHODS: Cell viability, apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry assays. The morphology of cancer cells was observed with inverted phase contrast microscope. The migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell assays. The expressions of poly (adenosine diphosphate-ribose) polymerase, C-Myc, Cyclin B1, cyclin-dependent kinases 1, N-cadherin, Vimentin, Active-β-catenin, β-catenin, p-glycogen synthase kinase 3β (GSK-3β) and GSK-3β were determined by Western blotting assay. RESULTS: PPI sensitized TRAIL-induced decrease of viability, migration and invasion, as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma cells. The synergistic effect of PPI with TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling pathway. CONCLUSION: The combination of PPI and TRAIL is potentially a novel treatment strategy of osteosarcoma.
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.
