DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for uterine sarcoma — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleUterine sarcoma maps to a 2-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 uterine 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
DNA topoisomerase II alpha (TOP2A) — TOP2A 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 5s,5ar,8ar,9rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZY5 · 3.6 Å · ligand (5S,5aR,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol
-5-yl 4,6-O-[(1R)-ethylidene]-beta-D-glucopyranoside (EVP). Experimental structure, not a prediction.
What the evidence adds up to
Uterine sarcoma is a rare and aggressive group of tumours with no standardised treatment established across its histologic types. A 2009 review states that surgery remains the mainstay of treatment with curative potential, but that effective adjuvant therapy to prolong survival has not yet been established, and that neither radiation nor different combinations of cytotoxic chemotherapy are likely to have a major impact on the course of the disease. A 2021 narrative review confirms that uterine sarcomas are very rare, extremely aggressive, and often associated with poor outcomes.
Survival figures from several retrospective studies are consistently poor. A 1997 study of 36 patients in Israel reported an overall 5-year survival rate of 32%, with 63% for endometrial stromal sarcoma, 30% for mixed mesodermal sarcoma, and 18% for leiomyosarcoma; only the difference between endometrial stromal sarcoma and leiomyosarcoma was statistically significant. A 2014 study of 36 patients in Saudi Arabia reported a 2-year disease-free survival rate of 22% and a 5-year rate of 14%, with only 30% of patients surviving 2 years overall. In that study, advanced stage and lymphovascular invasion were associated with poorer disease-free survival, while the use of chemotherapy was associated with improved disease-free survival. A 1987 study of 86 patients reported disease-free survivals of 40% with surgery alone, 53% with surgery plus chemotherapy, and 46% with surgery plus radiation with or without chemotherapy, but these differences were not statistically significant; local failure rates were 43%, 32%, and 33% respectively.
The 1997 study noted that 30.6% of patients received surgery alone, 11.1% surgery plus pelvic radiotherapy, 30.6% surgery plus chemotherapy, and 22.2% surgery plus both radiotherapy and chemotherapy. The 2014 study reported that 69% of patients received adjuvant chemotherapy and 14% received adjuvant radiotherapy. The 1987 study found that the most important prognostic factor was the clinical extent of the tumour. The 2009 review emphasises that because no adjuvant therapy has been shown to prolong survival, alternative approaches such as molecularly targeted therapies need to be explored.
What is still missing are large, prospective, randomised trials that can establish a standard adjuvant regimen for any histologic subtype. The rarity and heterogeneity of uterine sarcomas make such trials difficult to fund and complete. Patient stratification by histologic type and molecular markers is not yet routine, and no targeted therapy has been proven effective in a phase III setting.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Obstetrics & Gynecology · 2009 · 45 citations
Update on treatment of uterine sarcoma
AbstractPURPOSE OF REVIEW: Uterine sarcoma is a rare but extremely aggressive subtype of uterine malignancy. This heterogeneous group of tumors consists of several histologic types, including carcinosarcoma, leiomyosarcoma, and endometrial stromal sarcoma. Because of tumor rarity and histopathologic diversity, no standardized treatment for any histologic type has yet been established. In this review, we discuss recent studies and update the management of uterine sarcomas. RECENT FINDINGS: The recent trend is to treat each histologic type separately. New International Federation of Obstetrics and Gynecology staging systems unique to each histologic type have been developed. Prospective and retrospective studies have focused primarily on adjuvant therapy after surgical resection. SUMMARY: Surgery remains the mainstay of treatment for uterine sarcoma, demonstrating a curative potential regardless of histologic type. Effective adjuvant therapy to prolong survival has not yet been established. Because neither currently available radiation therapy nor different combinations of cytotoxic chemotherapeutic agents is likely to have a major impact on the course of uterine sarcoma, alternative approaches such as molecularly targeted therapies need to be explored.
Journal of Surgical Oncology · 1997 · 16 citations
Uterine sarcoma in the south of Israel: Study of 36 cases
AbstractBACKGROUND: Uterine sarcomas are rare, charaterized by rapid clinical progression and poor prognosis, and their management has been a challenge. The purpose of this study was to investigate the clinical and histologic findings, treatment, and outcome of patients with uterine sarcoma in the south of Israel. METHODS: Data from the files of 36 patients with uterine sarcoma who were managed at the Soroka Medical Center between January 1961 and December 1994 were evaluated. RESULTS: The 5-year survival rate was 32% overall; 63% for 9 patients with endometrial stromal sarcoma (ESS). 30% for 14 patients with mixed mesodermal sarcoma (MMS) and 18% for 13 patients with leiomyosarcoma (LMS): 41% for 22 patients with Stage I and 19% for 14 patients with Stages II, III, and IV. Only the difference in the 5-year survival rate between ESS and LMS was statistically significant (P < 0.05). Eleven patients (30.6%) were treated with surgery alone, 4 (11.1%) with surgery followed by pelvic radiotherapy, 11 (30.6%) with surgery followed by chemotherapy, 8 (22.2%) with surgery followed by pelvic radiotherapy and chemotherapy, one (2.8%) with chemotherapy alone, and one (2.8%) had no treatment. CONCLUSIONS: Uterine sarcomas are aggressive tumors with a poor prognosis. The treatment is surgery generally followed by adjuvant pelvic radiotherapy and/or systemic chemotherapy.
Saudi Medical Journal · 2014 · 15 citations · open access
Uterine sarcoma. Clinico-pathological characteristics and outcome
AbstractOBJECTIVES: To investigate the clinical and histopathological characteristics, with the prognostic factors, treatment outcome, pattern of relapse, and survival analysis of uterine sarcoma patients. METHODS: All patients with histologically proven uterine sarcoma were identified using the database at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between January 2000 and December 2012. RESULTS: A total of 36 patients with uterine sarcoma were reviewed. The median age of all patients was 57 years, and the mean age was 57.72+/-13.17 years. Carcinosarcoma was reported in 21 patients (58%), leiomyosarcoma in 7 (19%), undifferentiated endometrial sarcoma in 6 (17%), and rhabdomyosarcoma in 2 (6%). Approximately half of the patients were stages III and IV (28% and 25%), while 15 patients (41%) were stage I; only 2 patients (6%) were stage II. The surgical treatment was hysterectomy and bilateral salpingoophorectomy (H+BSO) plus staging in 18 patients (50%), while in 4 patients (19%), H+BSO plus debulking was performed. Adjuvant chemotherapy was given in 24 (69%) and adjuvant radiotherapy in 5 (14%) cases, At a median follow-up period of 13.5 months, 8 patients (22%) relapsed. The 2-year disease-free survival (DFS) rate was 22% and the 5-year was 14%. In the multivariate analysis, the advanced stages (p=0.015) and lymph vascular invasion (p=0.0001) were associated with poor DFS, while the use of chemotherapy significantly improved the DFS (p=0.027). CONCLUSIONS: The poor outcome of high-grade uterine sarcoma patients was identified, and only one third of patients (30%) survived for 2 years. This finding necessitates the need for more aggressive tools to fight this disease.
AbstractFrom 1965 to 1982, 86 analyzable patients with uterine sarcoma were treated. Nineteen patients (22%) presented with advanced disease. For the patients with curable diseases (67 patients), the disease-free survivals with a median follow-up of 4.5 years are 40% (surgery only), 53% (surgery + chemotherapy), 46% (surgery + radiation +/- chemotherapy). The local failure rates are 43%: 32%: 33%, respectively. There is no statistical significance. The most important prognostic factor is the clinical extent of the tumor. The role of radiation therapy and chemotherapy will be discussed.
Gynecology and Pelvic Medicine · 2021 · 2 citations · open access
Chemotherapy and uterine sarcomas: a narrative review
AbstractBackground and Objective: Uterine sarcomas are very rare, extremely aggressive, and often associated with poor outcomes. They include different histological variants, Leiomyosarcoma being the most common one and the most represented uterine sarcoma in clinical studies. We have reviewed the medical treatment of uterine sarcomas focusing on the available options for adjuvant therapy and for advanced, metastatic or recurrent disease, including the new targeted therapies that are currently being developed. Methods: A MEDLINE (PubMed) search of the literature was performed, focusing on papers published in the last two decades.
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.
