DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for chondrosarcoma — screening already-approved drugs against its 28-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleChondrosarcoma maps to a 28-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 chondrosarcoma 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
A-kinase anchoring protein 7 (AKAP7) — AKAP7 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 mlidrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5JJ2 · 1.25 Å · ligand MALONATE ION (MLI). Experimental structure, not a prediction.
What the evidence adds up to
In a single-institution retrospective review of 125 chondrosarcoma patients who underwent surgery, overall survival was 91.6% at 5 years, 84.1% at 10 years, and 84.1% at 15 years. The dedifferentiated histological type showed the worst survival. Among conventional-type chondrosarcoma, high-grade tumours in axial locations had the worst outcome, while low-grade chondrosarcoma of the appendicular skeleton could be treated safely by intralesional curettage.
Chondrosarcomas are in general resistant to chemotherapy and radiotherapy. The prognosis for patients with unresectable or metastatic disease is poor. Multiple oncogenic pathways have been identified, including isocitrate dehydrogenase mutations, hedgehog signalling, alterations in the retinoblastoma protein and p53 pathways, apoptosis and survival mechanisms, and several tyrosine kinases. These represent potential druggable targets.
Isocitrate dehydrogenase-1 and isocitrate dehydrogenase-2 mutations have been described in chondrosarcomas and serve as an identifying marker of chondroid differentiation. New compounds targeting these mutations have been developed and are being tested in preclinical models and clinical trials. However, the results of clinical studies evaluating targeted therapies in chondrosarcoma have so far been largely disappointing. Because chondrosarcoma is an orphan disease, all studies are performed with small numbers of patients.
What is still missing is adequate funding for larger multicentre trials, better patient stratification by histological subtype and molecular profile, and the translation of preclinical target discoveries into therapies that show consistent clinical benefit rather than disappointing results in small studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 1998 · 296 citations · open access
Primary chondrosarcoma of long bones and limb girdles
AbstractBACKGROUND: Chondrosarcomas are common solid malignant tumors of bone, second in incidence only to osteosarcomas. The biologic evolution of chondrosarcomas is slow, requiring long follow-up intervals for meaningful survival analysis. METHODS: This study describes the clinicopathologic profiles of 344 patients, 194 male and 150 female (M:F, 1.3:1.0), with primary chondrosarcoma of long bones and limb girdles seen at 1 institution over a period of 80 years. RESULTS: The average age at presentation was 46 years (range, 5-82 years). The pelvis was the most common location (1.7% of all patients). Local pain was the most frequently reported initial symptom (81.4%). Survival analysis was limited to 233 patients whose primary treatment was given at the Mayo Clinic. All 233 patients had potential follow-up of at least 5 years. The overall 5-year survival rate was 77% (the expected rate was 96%). Local recurrence developed in 19.7% of patients and metastatic lesions in 13.7%. The recurrence rate was higher for tumors of the shoulder and pelvis than for tumors of long bones. Radiographically, chondrosarcomas had a characteristic appearance, including a combination of bone expansion and cortical thickening. Entering the tumor at surgery increased the risk of local recurrence. Histologic tumor grade was an important predictor of local recurrence and metastasis. CONCLUSIONS: With adequate initial surgical intervention, chondrosarcoma is primarily a local disease with a low metastatic rate.
Cancer Research and Treatment · 2015 · 68 citations · open access
Long-term Outcome of Chondrosarcoma: A Single Institutional Experience
AbstractPURPOSE: The prognostic factors of chondrosarcoma remain uncertain as only a few large studies with long-term follow-up have been reported. The aim of this study was to analyze oncological outcomes and prognostic factors. MATERIALS AND METHODS: A retrospective review of oncological outcomes and prognostic factors was performed on 125 consecutive chondrosarcoma patients who underwent surgery at our institution. RESULTS: Overall survival was 91.6%±2.5%, 84.1%±3.8%, and 84.1%±3.8% at 5, 10, and 15 years respectively. Among the histological types, dedifferentiated type showed the worst survival (p < 0.001). As for conventional type chondrosarcoma, histologic grade and anatomical location predicted outcome, with high-grade with axial location having the worst outcome (p < 0.001). In contrast, low-grade chondrosarcoma of appendicular skeleton could be treated safely by intralesional curettage. CONCLUSION: Histological type was significantly associated with the outcome of chondrosarcoma. For the conventional type, histologic grade and anatomical location predicted outcome, with high-grade with axial location having the worst outcome.
Molecular oncogenesis of chondrosarcoma: impact for targeted treatment
AbstractPURPOSE OF REVIEW: The prognosis of patients with unresectable or metastatic chondrosarcoma of the bone is poor. Chondrosarcomas are in general resistant to chemotherapy and radiotherapy. This review discusses recent developments in the characterization of molecular pathways involved in the oncogenesis of chondrosarcoma that should be explored to improve prognosis of patients with advanced chondrosarcoma. RECENT FINDINGS: The different oncogenic pathways for chondrosarcoma have become better defined. These include alterations in pathways such as isocitrate dehydrogenase mutation, hedgehog signalling, the retinoblastoma protein and p53 pathways, apoptosis and survival mechanisms, and several tyrosine kinases. These specific alterations can be employed for use in clinical interventions in advanced chondrosarcoma. SUMMARY: As many different genetic alterations in chondrosarcoma have been identified, it is of the utmost importance to classify druggable targets that may improve the prognosis of chondrosarcoma patients. In recent years an increased number of trials evaluating targeted therapies are being conducted. As chondrosarcoma is an orphan disease consequently all studies are performed with small numbers of patients. The results of clinical studies so far have been largely disappointing. Therapeutic intervention studies of these new targets emerging from preclinical studies are of highest importance to improve prognosis of chondrosarcoma patients with advanced disease.
Anticancer Research · 2017 · 42 citations · open access
Clinical Efficacy of Carbon Ion Radiotherapy for Unresectable Chondrosarcomas
AbstractBACKGROUND: Carbon ion radiotherapy has precise dose distribution and high biological effectiveness and is likely a promising therapy for patients with sarcomas. We evaluated the outcomes of carbon ion radiotherapy in patients with unresectable chondrosarcomas. PATIENTS AND METHODS: A retrospective analysis of 75 tumors in 73 patients treated with carbon ion radiotherapy was performed. There were 26 spinal, 38 pelvic, and 11 other types of tumors. Seventy conventional and five dedifferentiated chondrosarcomas were treated in 69 and four patients, respectively. RESULTS: The median follow-up period was 49.4 (range=6.4-146.4) months. The 5-year local control, overall survival, and disease-free survival rates were 53%, 53%, and 34%, respectively. By multivariate analysis, tumor volume and histological grade were significantly related to overall and disease-free survival. Five patients required surgical intervention because of adverse events in the bones. CONCLUSION: Carbon ion radiotherapy might be a treatment option for unresectable chondrosarcoma.
Isocitrate dehydrogenase mutations in chondrosarcoma
AbstractPURPOSE OF REVIEW: This article reviews the most recent developments and implications in regard to isocitrate dehydrogenase mutations in chondrosarcoma, a disease in which currently available systemic therapies have proven inefficacious, with an emphasis on how disruption in normal cellular metabolism plays a role in oncogenesis. RECENT FINDINGS: The development of acquired isocitrate dehydrogenase-1/isocitrate dehydrogenase-2 mutations has been described in multiple tumors and more recently in chondrosarcomas. The impact of these mutations has been the focus of multiple research efforts during the last years, allowing us to better understand the impact of the mutation, including its interaction with other proteins, changes in expression of genes involved in tumor genesis, the oncogenic potential of 2-hydroxyglutarate, the impact on cellular proliferation and differentiation, and the influence on the epigenetic state of cells owing to changes in DNA and histone methylation patterns. New compounds targeting the mutation have been developed. SUMMARY: This mutation is the first of its kind described in chondrosarcoma, serving as an identifying marker of chondroid differentiation, and becoming the first molecular target with potential anticancer effect, translating into the development of therapies targeting these mutations currently being tested further in preclinical models and clinical trials.
A promising role of noble metal NPs@MOFs in chondrosarcoma management
Abstractresults, challenges such as understanding the mechanisms of action and clinical translation remain, and the therapeutic effect of PTT and PDT on deep chondrosarcoma seems unsatisfactory. Future exploration, such as combined therapy and multiple MOF therapy, could unlock the full potential of noble metal NPs@MOFs in revolutionizing chondrosarcoma management, offering insights into the prospect of these materials in chondrosarcoma management.
Extraskeletal Mesenchymal Chondrosarcoma of Shoulder: An Extremely Rare Case.
AbstractINTRODUCTION: Extraskeletal chondrosarcoma (EMC) is a rare, aggressive neoplasm which has been seen in the soft tissue area. This soft tissue sarcoma is classified to myxoid and mesenchymal based on histologic criteria. The mesenchymal subtype has a poor prognosis. In approximately 50% of patient with EMC, we could observe soft tissue lesion and stippled calcification in the conventional radiography. CASE REPORT: In the current paper, we introduced a 47-year-old Iranian male patient having painless, mobile, nontender, and firm mass in left shoulder. We did not find neurovascular disturbance at the upper extremity, and the patient had a full range of motion in the left shoulder. The tumor was treated with wide resection and followed by radiation therapy. CONCLUSION: Complete wide resection of mesenchymal chondrosarcoma could be enough as an initial treatment and chemotherapy reserved for patients that have unresectable masses. Apparently, the main key in the treatment is the surgical resection, and this process is the most important method in their management.
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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