DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for 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 moduleSarcoma 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
Structures already discussed alongside sarcoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 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 b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 case report describes a 49-year-old woman with follicular dendritic cell sarcoma of the neck, a rare sarcoma with metastatic potential. After complete excision of the cervical lymph node, she received five courses of adjuvant chemotherapy with COP (cyclophosphamide, vincristine, prednisone) plus PEG-liposomal doxorubicin. No haematological or cardiac toxicity occurred; only transient palmar erythrodysesthesia was noted. At five years of follow-up she remained alive and in complete remission. The report is a single case, not a trial.
A 1989 study of 22 adults with osteosarcoma (median age 37) found that among six patients treated with complete resection followed by adjuvant chemotherapy, four remained continuously disease-free at 25+, 29+, 72+, and 75+ months. Among eight patients who had complete resection without adjuvant chemotherapy, four were disease-free for more than two years (31, 33, 44, 44+ months), but only one remained continuously disease-free. The authors note that many patients had advanced-stage, poor-prognosis lesions and require alternative approaches. Adults tolerated chemotherapy well.
A 2023 review of local therapies for metastatic sarcoma states that management has evolved from a one-size-fits-all approach to a more personalised, multidisciplinary strategy. It reports that local treatments (radiotherapy, surgery, interventional radiology) have contributed to improved survival in advanced sarcoma, but provides no new trial data or specific survival numbers.
What is still missing are prospective randomised trials testing the COP plus liposomal doxorubicin regimen in follicular dendritic cell sarcoma, larger studies of adjuvant chemotherapy in adult osteosarcoma with stratification by primary site and resectability, and controlled evidence that local therapies improve overall survival rather than just progression-free intervals in metastatic sarcoma. Funding for such trials remains scarce.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Expert Opinion on Pharmacotherapy · 2013 · 53 citations
Pazopanib, a new therapy for metastatic soft tissue sarcoma
AbstractINTRODUCTION: Pazopanib (GW786034, Votrient®) is a vascular endothelial growth factor receptor-focused multi-tyrosine kinase inhibitor involved in inhibiting the angiogenesis pathway. The agent was recently registered for use in soft tissue sarcomas, a group of diseases with a major unmet medical need. AREAS COVERED: The relevance of angiogenesis in soft tissue sarcomas is discussed. These data were the basis to decide on the development of pazopanib in these diseases. The clinical pharmacology of pazopanib, as far as practically relevant, is summarized. After the first observations of possible activity in soft tissue sarcomas in the Phase I study, a Phase II and subsequent randomized placebo-controlled Phase III study were performed and are being put into perspective in this review. EXPERT OPINION: Pazopanib is an active drug for the treatment of chemotherapy-failing nonadipocytic soft tissue sarcomas. It almost triples progression-free survival significantly from 1.6 to 4.6 months in this heavily pretreated population. The safety profile is manageable, exemplified by the high dose intensity that can be achieved over time. Pazopanib can be considered as part of the standard of care for patients with soft tissue sarcomas.
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.
Clinical Orthopaedics and Related Research · 1989 · 15 citations
Osteosarcoma in Adults
AbstractTwenty-six patients were referred to the adult sarcoma clinic of the authors' institution between 1979 and 1986. The diagnosis was not confirmed in four patients. The median age of the 22 confirmed patients was 37. Twelve patients had central skeletal primaries; of these 12, seven had metastatic or unresectable disease. Six patients were treated with complete resection of tumor followed by adjuvant chemotherapy; of these six, four remained continuously disease-free at 25+, 29+, 72+, and 75+ months. Eight patients received no adjuvant chemotherapy following complete resection. Four have remained disease-free for more than two years (31,33,44,44+ months); however, only one remains continuously disease-free. Adults tolerated chemotherapy well and should be considered appropriate candidates for adjuvant trials. Many, however, will have advanced-stage, poor-prognosis lesions and require alternative approaches for treatment.
American Journal of Therapeutics · 2010 · 15 citations
Treatment of Multidrug Resistant Advanced Alveolar Soft Part Sarcoma With Sunitinib
AbstractSunitinib is a tyrosine kinase/angiogenesis inhibitor with proven efficacy in gastrointestinal stromal tumor and advanced renal cell carcinoma. We are presenting the case report of a patient with aggressive alveolar soft part sarcoma with lung and bone metastases, who had failed multiple chemotherapy regimens showing significant response to sunitinib. There was not only complete regression of the primary tumor, stabilization of his bone metastases and significant improvement in the quality of life. Our report shows that sunitinib has the capability of playing a pivotal role in the management of non-gastrointestinal stromal tumors like alveolar soft part sarcoma. Further research and trials must be encouraged over the use of this drug as it is most definitely promising.
Frontiers in Oncology · 2021 · 10 citations · open access
Crizotinib in Sarcomatous Malignancies Harboring ALK Fusion With a Definitive Partner(s): Response and Efficacy
AbstractSarcoma or sarcomatoid malignancies are a set of mesenchymal-origin malignancies with vast heterogeneity in clinical and molecular characteristics. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase oncoprotein expressed by several tumors, including sarcomas. Crizotinib is an effective ALK inhibitor. In this review paper, we summarized findings from the literature regarding the use of crizotinib for the treatment of sarcoma and sarcomatoid malignancies harboring ALK fusions with definitive partners (with the given gene(s) name) from the years 2010 to 2021.One hundred and four articles were retrieved and after exclusion, 28 studies containing 33 patients were finally selected. All 33 patients were treated with crizotinib. Among the 33 cases, 19 were adult patients, 11 were pediatric patients, and 3 cases did not have data on age and/or gender. Most cases had a primary abdominal lesion (16/30), followed by thoracic (10/30), trunk (3/30), retroperitoneal (1/30), and one case of right medial thigh (case 7). Stage IV disease was reported in 76.7% (23/30) of patients. The objective response rate and disease control rate was 86.7% (26/30) and 96.7% (29/30), respectively, which were assessed on average of 8 weeks after crizotinib initiation. Rapid improvement of symptoms was observed within one to two weeks in some cases including patients with extensive diseases or poor performance. There was no difference in crizotinib response between pediatrics and adult cases. Crizotinib is effective; however, surgery remains the mainstay of therapy, with newer evidence showing concurrent crizotinib with surgery conferring long-term overall survival. However, we should still be cognizant of the heterogeneous landscape of crizotinib efficacy and its associated fatal adverse events.
American Society of Clinical Oncology Educational Book · 2023 · 6 citations · open access
Local Therapies for Metastatic Sarcoma: Why, When, and How?
AbstractManagement of patients with advanced sarcoma has been evolving in recent decades, from a one-fit-all perspective to a more refined, personalized, and multidisciplinary approach. In parallel, the evolution of local therapies (radiotherapy, surgical and interventional radiology techniques) has contributed to the improvement of survival of patients with advanced sarcoma. In this article, we review the evidence regarding local treatments in advanced sarcoma, as well as its integration with systemic therapies, to provide the reader a wider and deeper perspective on the management of patients with metastatic sarcoma.
Abstract† Five cases of Kaposi sarcoma with vinblastine sulfate treatment were compared with 18 cases reported in the literature. Our experience with a low-dosage schedule emphasizes that toxicity is not necessary for a favorable result. Vinblastine seems to be an effective treatment for Kaposi sarcoma and, in selected cases, may supplement radiation therapy or be used alone. (<i>Arch Dermatol</i>112:958-961, 1976)
Anticancer Research · 2024 · 4 citations · open access
Recombinant Methioninase Increases Eribulin Efficacy 16-fold in Highly Eribulin-resistant HT1080 Fibrosarcoma Cells, Demonstrating Potential to Overcome the Clinical Challenge of Drug-resistant Soft-tissue Sarcoma
AbstractBACKGROUND/AIM: A major challenge in treating soft-tissue sarcoma is the development of drug resistance. Eribulin, an anti-tubulin agent, is used as a second-line chemotherapy for patients with unresectable or metastatic soft-tissue sarcoma. However, most patients with advanced soft-tissue sarcoma are resistant to eribulin and do not survive. Recombinant methioninase (rMETase) targets the fundamental and general hallmark of cancer, methionine addiction, termed the Hoffman Effect. The present study aimed to show how much rMETase could increase the efficacy of eribulin on eribulin-resistant fibrosarcoma cells in vitro. MATERIALS AND METHODS: HT1080 human fibrosarcoma cells were exposed to step-wise increasing concentrations of eribulin from 0.15-0.4 nM to establish eribulin-resistant HT1080 (ER-HT1080). ER-HT1080 cells were cultured in vitro and divided into four groups: untreated control; eribulin treated (0.15 nM); rMETase treated (0.75 U/ml); and eribulin (0.15 nM) plus rMETase (0.75 U/ml) treated. RESULTS: of rMETase on ER-HT1080 and HT1080 was 0.87 U/ml and 0.75 U/ml, respectively. The combination of rMETase (0.75 U/ml) and eribulin (0.15 nM) was synergistic on ER-HT1080 cells resulting in an inhibition of 80.1% compared to eribulin alone (5.0%) or rMETase alone (47.1%) (p<0.05). rMETase thus increased the efficacy of eribulin 16-fold on eribulin-resistant fibrosarcoma cells. CONCLUSION: The present study showed that the combination of eribulin and rMETase can overcome high eribulin resistance of fibrosarcoma. The present results demonstrate that combining rMETase with first- or second-line therapy for soft-tissue sarcoma has the potential to overcome the intractable clinical problem of drug-resistant soft-tissue sarcoma.
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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