DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for clear cell sarcoma — screening already-approved drugs against its 24-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleClear cell sarcoma maps to a 24-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 clear cell sarcoma 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
Clear cell sarcoma is a rare soft tissue tumour. In a paediatric series from St. Jude Children’s Research Hospital covering 1962 to 1998, only 5 of 225 children with nonrhabdomyosarcomatous soft tissue sarcomas had clear cell sarcoma. Three patients with localised disease who underwent surgical resection, with radiotherapy in two cases and chemotherapy in one, survived disease-free at 10, 11, and 90 months. The two patients who already had metastatic disease at diagnosis died 21 days and 9 months later. The authors concluded that complete surgical resection with negative margins is the most effective treatment and that patients with metastatic disease should be entered into multi-institutional chemotherapy trials.
A 2010 retrospective study from two referral centres reported on 24 clear cell sarcoma patients treated with palliative first-line chemotherapy. All had initially undergone surgical resection of the primary tumour. At the time of analysis 22 patients had died and 2 were lost to follow-up. Among the 24 patients receiving chemotherapy for recurrent or metastatic disease, only one (4%) achieved a partial response, 9 (37%) had stable disease, and 14 (58%) progressed on therapy. Median progression-free survival was 11 weeks (95% CI, 3–20 weeks) and median overall survival from starting first-line chemotherapy was 39 weeks (95% CI, 34–45 weeks). Second-line chemotherapy was given to 12 patients: 11 (92%) progressed and one (8%) had stable disease. Of 5 patients who received third-line chemotherapy, 4 (80%) progressed and one (20%) had stable disease. One patient on fourth-line chemotherapy maintained stable disease for 4 months. The authors concluded that conventional chemotherapy has minimal activity in clear cell sarcoma.
A 2008 case report described a 49-year-old woman with follicular dendritic cell sarcoma of the neck, a different disease entity, who after complete excision received five cycles of adjuvant chemotherapy with COP plus PEG-liposomal doxorubicin. After 5 years of follow-up she was alive and in complete remission. This report does not concern clear cell sarcoma.
What is still missing are prospective trials large enough to test novel agents in this ultra-rare sarcoma, reliable biomarkers to stratify patients by expected chemotherapy resistance, and funding to move beyond the single-digit response rates documented here.
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 · 1978 · 26 citations · open access
Clear cell sarcoma with melanin.Report of two cases
AbstractTwo cases of clear cell sarcoma, one with many melanin pigmented cells and the other scanty, are described. Both are associated with tendons of the lower extremities of young Chinese adults. Their clinical behaviour differed vastly; one patient was dead seven months after local excision and block dissection of regional lymph nodes, while the other had a history of the growth of eight years prior to local excision and is well four years later.
Clinical and Experimental Dermatology · 2003 · 20 citations
Complete remission of metastatic clear cell sarcoma with DAV chemotherapy
AbstractWe report the first case of metastatic clear cell sarcoma with dramatic response to DAV treatment (DTIC + ACNU + VCR). Clear cell sarcoma of tendons and aponeuroses, or malignant melanoma of soft parts, is a rare tumour that occurs predominantly in the extremities of young adults. It tends to recur locally or metastasize and the prognosis is poor. Although the importance of surgery has been established, the role of adjuvant chemotherapy has yet to be determined. DAV should be considered as a first-line palliative treatment in disseminated disease as well as adjuvant therapy after surgery of primary clear cell sarcoma.
Pediatric Hematology and Oncology · 1999 · 17 citations
CLEAR CELL SARCOMA OF SOFT TISSUES IN CHILDREN AND YOUNG ADULTS: The St. Jude Children's Research Hospital Experience
AbstractClear cell sarcoma is a rare soft tissue neoplasm whose clinical behavior and outcome has not been previously characterized. This study reviewed the clinical characteristics and outcome of all children with clear cell sarcoma of the soft tissues who were treated at St. Jude Children's Research Hospital from March 1962 through August 1998. Of 225 children with nonrhabdomyosarcomatous soft tissue sarcomas, 5 (2.2%) were diagnosed with clear cell sarcoma. Median age at diagnosis was 15 years 3 months. Primary sites included the extremities (n = 3), chest wall (n = 1), and abdomen (n = 1). At diagnosis 3 patients had localized disease. Following surgical resection (n = 3), radiotherapy (n = 2), and chemotherapy (n = 1) all three survive disease-free 10, 11, and 90 months after diagnosis, respectively. The remaining two patients with metastatic disease at diagnosis died 21 days and 9 months after diagnosis. Clear cell sarcoma of the soft tissues is rare in pediatrics. Complete surgical resection with negative margins is the most effective treatment for this disease. Patients with metastatic disease are candidates for multiinstitutional chemotherapy trials.
Journal of Experimental & Clinical Cancer Research · 2008 · 17 citations · open access
Follicular dendritic cell sarcoma of the neck: Report of a case treated by surgical excision and COP plus (PEG)-liposomal doxorubicin
AbstractBACKGROUND: Follicular dendritic cell (FDC) sarcoma is a rare neoplasm arising in lymph nodes but also in extranodal sites from accessory cells of the immune system that are essential for the function of antigen presentation and germinal center reaction regulation. FDC sarcoma has a significant recurrent and metastatic potential and for these reason it should be viewed as an intermediate grade malignancy. METHODS: We report the case of a 49-year old woman patient who showed persistent, enlarged, hard, cervical lymph node. The most common histologic feature was the presence of oval to spindle cells with elongated nuclei, vesicular or stippled chromatin and scant eosinophilic cytoplasm. Immunohistochemically, tumor cells were diffusely positive for follicular dendritic cell markers CD21, CD23 and negative for cytokeratin.The patient after complete excision of the lymph node underwent five courses of adjuvant chemotherapy with COP plus PEG-liposomal doxorubicin, considering the propensity of the tumor to metastasize. RESULTS: No hematological or cardiac toxicity were registered and among the other extra hematological effects only transitory palmar erythrodysesthesia is worthy of mention. After a follow up of 5 years the patient is alive and in CR. CONCLUSION: These results suggest that this therapeutic modality may be useful in the management of FDC sarcoma.
Abstract10098 Background: Clear cell sarcoma is a rare soft tissue sarcoma subtype associated with the characteristic translocation t(12;22)(q13;q12). There have been few studies documenting the response rate and progression-free survival in clear cell sarcoma patients treated with palliative chemotherapy. Methods: The prospectively maintained databases of two referral centres were searched to identify clear cell sarcoma patients treated with chemotherapy. Results: Twenty-four patients were treated with palliative first-line chemotherapy with a median age of 30 years at diagnosis. All patients underwent surgical resection of the primary tumour as initial management. At the time of analysis 22 patients had died and 2 were lost to follow-up. There were 18 males and 6 females. Two of these patients were treated with neoadjuvant chemotherapy at the time of initial diagnosis and received palliative systemic therapy on progression. One of these achieved a partial response and the response of the other to neoadjuvant therapy was not known. For the patients receiving chemotherapy for recurrent/metastatic disease (n=24), one (4%) achieved a partial response and 9 (37%) had stable disease. Fourteen patients (58%) progressed on therapy. The median progression-free survival was 11 weeks (95%CI, 3-20 weeks). The median overall survival from commencing first-line chemotherapy was 39 weeks (95%CI, 34-45 weeks). Second-line chemotherapy was administered to 12 patients, 11 (92%) of these progressed and one (8%) had stable disease. Of the 5 patients treated with third-line chemotherapy, 4 (80%) progressed and one (20%) had stable disease. One patient that received fourth-line chemotherapy maintained stable disease for 4 months. Conclusions: Conventional chemotherapy has minimal activity in clear cell sarcoma as documented by the response rate of 4% and median progression-free survival of 11 weeks in this retrospective series. These data provide a reference for response and outcome in the assessment of novel agents in this histological subtype. No significant financial relationships to disclose.
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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