DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for synovial sarcoma — screening already-approved drugs against its 47-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSynovial sarcoma maps to a 47-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
approvedPazopanibApproved drug
Structures already discussed alongside synovial sarcoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
HRas proto-oncogene, GTPase (HRAS) — HRAS is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has phosphoaminophosphonic acid-guanylate ester bound in it, shown as sticks.
Loading structure…
helix sheet gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ELT · 1.66 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
In a series of 121 consecutive synovial sarcoma patients treated at two referral centres, the estimated 5‑, 10‑, and 15‑year survival rates were 60%, 50%, and 45% respectively. Local recurrence occurred in 31% of patients, and 54% developed metastasis, predominantly to the lungs. Independent risk factors for tumour‑related death were older age, poor histologic differentiation, and larger tumour size. A low‑risk group (age <25 years, tumour size <5 cm, no poorly differentiated histology) had 88% overall disease‑free survival, while a high‑risk group (age ≥25 years, tumour size ≥5 cm, poorly differentiated tumour) had 18% overall disease‑free survival. Local recurrence carried a 3.66‑fold increased risk of death.
In a paediatric and adolescent relapsed synovial sarcoma cohort of 41 patients treated between 2002 and 2022 at six European centres, first relapse occurred at a median of 18 months after diagnosis. Relapse was local in 34%, metastatic in 54%, and both in 12%. At first relapse, 56% had surgery, 34% radiotherapy, and 88% systemic therapy. Among 36 patients who received second‑line medical treatment, 32 received chemotherapy across ten different regimens and four received targeted therapy. No patient entered an early‑phase clinical trial as second‑line therapy. The overall response rate was 42%. Median event‑free survival after relapse was 12 months, with a 5‑year event‑free survival of 15.8%. Median overall survival after relapse was 30 months, with a 5‑year overall survival of 22.2%. Overall survival was significantly associated with time and type of relapse.
A case report of a 32‑year‑old woman with an unresectable mediastinal synovial sarcoma showed no response to three cycles of ifosfamide and doxorubicin; the patient refused further therapy and progressed four months after the last cycle. Another case series described four patients, including one whose primary tumour was initially misdiagnosed as a Baker’s cyst and who died 11 months after diagnosis of an intracranial metastasis from an angioinvasive synovial sarcoma. In a separate virological study of 41 synovial sarcoma specimens, no DNA of EBV, HHV‑8, or HPV was detected by PCR.
What remains missing are prospective trials that stratify patients by the risk groups already identified, a standardised approach to relapsed disease, and early‑phase clinical trial access for children and adolescents after relapse. The biological drivers of synovial sarcoma, beyond the known translocation, are still poorly understood, and no effective targeted therapy has emerged from the small, heterogeneous series reported to date.
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 · 1999 · 294 citations · open access
Synovial sarcoma
AbstractBACKGROUND: Synovial sarcoma, one of the most common soft tissue sarcomas that occur in adolescents and young adults, is generally viewed and treated as a high grade sarcoma. However, the authors' own experience and some previous studies have indicated that it has a wide spectrum of biologic behavior and that low and high risk subgroups of patients with synovial sarcoma can be identified. METHODS: A total of 121 consecutive patients with synovial sarcoma (including 66 males and 55 females ages 9-74 years), treated primarily or secondarily at 2 large referral centers for musculoskeletal tumors, were included in a statistical analysis conducted to identify independent prognostic factors. RESULTS: There were local recurrences in 38 patients (31%), usually after inadequate primary surgery outside the referral centers; 64 patients (54%) developed metastasis, primarily to the lungs. The estimated 5-, 10-, and 15-year survival rates were 60%, 50%, and 45%, respectively (the mean follow-up for surviving patients was 9.8 years, with a range of 1-30 years). In multivariate analysis, independent risk factors for local recurrence included larger tumor size and primary surgical resection outside the referral center. Independent risk factors for metastasis were older patient age, tumor with poor histologic differentiation, and tumor necrosis. For tumor-related death, the independent risk factors were older patient age, tumor with poor histologic differentiation, and larger tumor size. Local recurrence was associated with a 3.66-fold increased risk of tumor-related death. A low risk group (patient age <25 years, tumor size <5 cm, and no histologic evidence of poorly differentiated tumor) with 88% overall disease free survival was identified, as was a high risk group (patient age > or = 25 years, tumor size > or = 5 cm, and poorly differentiated tumor) with 18% overall disease free survival (P < 0.001). CONCLUSIONS: The identification of low and high risk synovial sarcoma patients indicates that synovial sarcomas are not uniformly high grade tumors. It also indicates that treatment strategies should be modified for these risk groups. Adequate primary surgery is essential to both local control and outcome for synovial sarcoma patients.
BMC Research Notes · 2013 · 13 citations · open access
Synovial sarcoma presenting with huge mediastinal mass: a case report and review of literature
AbstractBACKGROUND: Synovial sarcoma presenting in the mediastinum is exceedingly rare. Furthermore, data addressing optimal therapy is limited. Herein we present a case where an attempt to downsize the tumor to a resectable state with chemotherapy was employed. CASE PRESENTATION: A 32 year female presented with massive pericardial effusion and unresectable huge mediastinal mass. Computed axial tomography scan - guided biopsy with adjunctive immunostains and molecular studies confirmed a diagnosis of synovial sarcoma. Following three cycles of combination Ifosfamide and doxorubicin chemotherapy, no response was demonstrated. The patient refused further therapy and had progression of her disease 4 months following the last cycle. CONCLUSION: Synovial sarcoma presenting with unresectable mediastinal mass carry a poor prognosis. Up to the best of our knowledge there are only four previous reports where primary chemotherapy was employed, unfortunately; none of these cases had subsequent complete surgical resection. Identification of the best treatment strategy for patients with unresectable disease is warranted. Our case can be of benefit to medical oncologists and thoracic surgeons who might be faced with this unique and exceedingly rare clinical scenario.
Clinical Sarcoma Research · 2015 · 3 citations · open access
Do human tumor-associated viruses play a role in the development of synovial sarcoma?
AbstractBACKGROUND: To date, the pathomechanism of soft tissue sarcomas such as synovial sarcoma remains unclear whereas even a viral etiology was suspected. Aim of this study was to analyze whether EBV, HHV-8 or HPV play a role in the development of synovial sarcomas. FINDINGS: In total 41 synovial sarcomas were included in this retrospective study. For detection of EBV 1/2 and HHV-8, resection specimens were analyzed with regard to virus-specific sequences using a SingleStep PCR. HPV analysis was carried out by an HPV-specific multiplex-PCR and subsequent array-hybridization for HPV-typing. No virus-specific DNA of EBV, HHV-8 or HPV was detected. CONCLUSION: An involvement of these viruses in the etiology of synovial sarcoma was not detected but further studies are needed with different virus types and sarcoma entities.
Zentralblatt für Chirurgie - Zeitschrift für Allgemeine Viszeral- Thorax- und Gefäßchirurgie · 2003 · 2 citations
Das Synovialsarkom in der klinischen Praxis - eine Zusammenstellung ausgesuchter Fälle
AbstractUNLABELLED: Clinically, synovial sarcoma becomes apparent as a growing mass. Initial presentation and the course may be variable. We discuss 4 characteristic patients. CASE 1: A 37 year-old female patient presented with a mass in her thigh after two consecutive resections of a malignant hemangioendothelioma. HISTOLOGY: Biphasic synovial sarcoma (G II). CASE 2: A tumor was enucleated in the adductors of a 42 year-old female patient. HISTOLOGY: Biphasic synovial sarcoma (G I). 2 years later local tumor recurrence (G I) occurred. Treatment was provided by wide resection and radiotherapy. CASE 3: Resection of a suspected neurinoma in the thigh of a 34 year-old male patient. HISTOLOGY: Biphasic synovial sarcoma, positive margins. CASE 4: A 74 year- old female patient receiving anticoagulants was symptomatic due to intracranial tumor hemorrhage of a metastasis of a previously unknown synovial sarcoma of her popliteal fossa. The primary tumor was initially misdiagnosed as Baker's cyst, causing a deep vein thrombosis. HISTOLOGY: Angioinvasive synovial sarcoma (G II). Survival: 11 months. THERAPY: Wide resection and postoperative irradiation in cases 1-3. Indication for the irradiation in case 2 and 3 was due to the inadequate operation. An amputation was performed in case 4 because of infiltration of the neurovascular structures. CONCLUSION: The presentation of synovial sarcoma does not differ from other soft tissue sarcomas. Patients should be treated in specialized centers to reduce inadequate operations. Outcome and rate of metastatic disease suggest the need for improved adjuvant treatment modalities.
Annals of Oncology · 2018 · 2 citations · open access
Pazopanib in advanced or metastatic synovial sarcoma: The Gustave Roussy experience
AbstractBackground: Synovial sarcoma (SS) is a rare malignancy usually considered as sensitive to chemotherapy (CT) based on anthracyclins and ifosfamide. Therapeutic options are limited and prognosis of advanced or metastatic SS (a/mSS) remains dismal. Since approval of pazopanib in advanced soft tissue sarcomas (STS), very few data were reported on the activity of pazopanib in a/mSS.
Pediatric Blood & Cancer · 2024 · 1 citations · open access
Treatment at relapse for synovial sarcoma of children and adolescents: A multi‐institutional European retrospective analysis
AbstractPURPOSE: Though the prognosis for pediatric patients with localised synovial sarcoma (SS) is generally good, the chances of being cured after relapse are limited. This study describes a retrospective multi-institutional series of relapsing SS patients treated at six selected European referral centers for pediatric sarcoma. PATIENTS AND METHODS: The study included 41 patients <21 years with relapsing SS, treated between 2002 and 2022. The analysis included patient's characteristics at first diagnosis, first-line treatments, clinical findings at relapse, and second-line treatment modalities. RESULTS: The first relapse occurred within 3-132 months (median 18 months) after first diagnosis and was local in 34%, metastatic in 54%, and both in 12%. Treatment at first relapse included surgery in 56% of cases, radiotherapy in 34%, and systemic therapy in 88%. In all, 36 patients received second-line medical treatment, that was chemotherapy in 32 cases (with 10 different regimens) and targeted therapy in four. No patient was included in an early-phase clinical trial as second-line therapy-line therapy. Overall response rate was 42%. Median event-free survival (EFS) was 12 months, postrelapse 5-year EFS was 15.8%. Median overall survival (OS) was 30 months, postrelapse 5-year OS was 22.2%. At the Cox's multivariable regression analysis, OS was significantly associated with time and type of relapse. CONCLUSION: Pediatric patients with relapsed SS have a poor prognosis and generally receive an individualized approach, due to the lack of a uniform standardized approach. New comprehensive strategies are needed to improve the knowledge on the biologic landscape of SS and develop tailored prospective clinical trials.
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.
