DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Uterine Carcinosarcoma — 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 moduleUterine Carcinosarcoma 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 uterine carcinosarcoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Cbl proto-oncogene B (CBLB) — CBLB 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 3-[3-[3-methyl-1-(4-methyl-1,2,4-triazol-3-yl)cyclobutyl]phenyl]-5-(trifluoromethyl)-1~{h}-pyridin-2-one bound in it, shown as sticks.
Loading structure…
helix sheet 4-methyl-1,2,4-triazol-3-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8QTG · 1.419 Å · ligand 3-[3-[3-methyl-1-(4-methyl-1,2,4-triazol-3-yl)cyclobutyl]phenyl]-5-(trifluoromethyl)-1~{H}-pyridin-2-one (WUQ). Experimental structure, not a prediction.
What the evidence adds up to
Uterine carcinosarcoma is a rare malignancy with an incidence of 1 to 4 per 100,000 women in the United States. Median survival is less than 2 years. In a retrospective study of 29 patients treated between 2007 and 2012, median follow-up was 13 months; 17 patients (59%) relapsed and 20 patients (69%) died. All recurrences were fatal. Three-year relapse-free survival was 31% and three-year overall survival was 15%. At diagnosis, 38% of patients had stage IV disease. Another study notes that between 25 and 30% of women already have distant metastases or positive lymph nodes at diagnosis.
Surgery remains the mainstay of treatment. Adjuvant radiotherapy may improve loco-regional control but does not change survival. In the 29-patient cohort, 20 patients (69%) received chemotherapy, 90% of them with paclitaxel and carboplatin for six cycles; one patient received radiotherapy. Despite this, prognosis was poor. The authors state that more effective adjuvant strategies are needed because recurrences are generally fatal. A 2008 review notes that chemotherapy can extend life for patients with advanced, persistent, or recurrent disease, but its effect remains to be further enhanced.
Molecular studies have identified potential drivers. RNA-seq analysis of prospectively collected tumour samples found RACGAP1 highly upregulated in uterine carcinosarcoma. Functional assays showed that RACGAP1 mediates motility and invasion via STAT3 phosphorylation and survivin expression. In a TCGA cohort, RACGAP1 expression correlated with survivin expression and extrauterine spread. Separately, a 2025 study using defined genetic models found that combined inactivation of Fbxw7 and Pten in mice produced endometrioid adenocarcinomas that all eventually developed into uterine carcinosarcomas, with most tumours spontaneously acquiring Trp53 mutations. Lineage tracing showed the cell of origin is an endometrial epithelial cell that undergoes epithelial-mesenchymal transition driven by Fbxw7.
What is still missing is a standardised treatment protocol that improves survival beyond the current dismal figures. No targeted therapy directed at RACGAP1, STAT3, survivin, or Fbxw7 has been tested in patients with this disease. Prospective trials large enough to stratify by stage, molecular subtype, or surgical completeness are lacking, partly because the disease is rare and funding for dedicated trials is limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractCarcinosarcoma is a rare but highly aggressive uterine malignancy. Pathologically, carcinosarcoma is a biphasic neoplasm composed of a mixture of malignant epithelial and mesenchymal components. A comprehensive approach for management is recommended with complete surgical staging to assess tumor dissemination followed by multimodal therapy with combinations of external beam irradiation or vaginal brachytherapy and systematic chemotherapy in patients with both early and advanced stage disease.
Efficacy of pazopanib in FGFR1-amplified uterine carcinosarcoma: A case report
Abstract• We reported the use of pazopanib in the treatment of recurrent uterine carcinosarcoma with FGFR1 amplification. • The expert tumor board recommended pazopanib for off-label use based on genetic mutations found in cancer gene panels. • Pazopanib, a multi-tyrosine kinase inhibitor, was effective against recurrent uterine sarcoma with FGFR1 amplification. • Pazopanib maintained the patient’s quality of life for a certain period.
AbstractCarcinosarcoma(CS)of the uterus is a rare class of malignant female pelvic neoplasms.The primary modality of therapy for uterine CS is surgery.Postoperative adjuvant radiation therapy may only improve loco-regional control.Standard adiuvant treatment of uterine CS has shifted from primarily loco-regional radiotherapy to chemotherapy.Potentially more effective adjuvant chemotherapy regimens will be investigated.Chemotherapy can extend life for patients with advanced,persistent,or recurrent uterine CS.However,effect of chemotherapy remains to be further enhanced.
Key words:
Uterus; Carcinosarcoma; Radiotherapy; Drug therapy
Impact of treatment strategies on local control and survival in uterine carcinosarcomas.
Abstracte16526 Background: Carcinosarcoma is a biphasic neoplasm composed of a mixture of malignant epithelial and mesenchymal components. Uterine carcinosarcomas comprise only 3% of all uterine malignancies, however they account for a disproportionally higher rate of mortality from uterine cancer because of their agressive nature. No standardized treatment has yet been established. The purpose of this study was to determine the clinical characteristics, patterns of recurrence and survival outcomes in patients with uterine carcinosarcoma treated in our institution. Methods: Records of the patients with uterine carcinosarcoma were retrospectively evaluated and 29 pts with carcinosarcoma diagnosed between 2007 and 2012 were identified. All patients were initially treated surgically by the same surgeon with comprehensive staging, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy , bilateral pelvic and paraaortic lymph node dissection and omentectomy. Demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of relapse-free survival (RFS) and overall survival (OS) were analyzed. Results: Median age was 63 (range 43-78). 13 patients (45%) had stage I disease, 5 patients (17%) had stage III and 11 patients (38%) had stage IV disease at diagnosis. Median tumor size was 6 cm (range 1.7-20 cm) and lymphovascular invasion was present in 17 patients 59%). Twenty patients (69%) received chemotherapy (90% with paclitaxel and carboplatin) for 6 cycles. One patient received radiotherapy. Median follow up was 13 mos. Seventeen patients (59%) relapsed and 20 patients (69%) died on follow up. Two patients had vaginal cuff recurrence, 4 had pelvic, 4 had abdominal and 7 had distant recurrences. All recurrences were fatal. 3 year RFS was 31%. 3 year OS was 15%. Conclusions: Our data show that uterine carcinosarcomas tend to be more at more advanced stage at diagnosis and despite the use of chemotherapy and radiotherapy, overall prognosis is poor. Surgery remains the mainstay of treatment. More effective adjuvant strategies are needed to reduce relapse and death rates because recurrences are generally fatal.
Geburtshilfe und Frauenheilkunde · 2017 · 0 citations
Karzinosarkom des Uterus: Lymphadenektomie vs. Chemotherapie vs. Brachytherapie
AbstractSeagle BLL et al. Stage I uterine carcinosarcoma: matched cohort analyses for lymphadenectomy, chemotherapy, and brachytherapy. Gynecol Oncol 2017; 145: 71 – 77 Zwischen 25 und 30% der vom Karzinosarkom des Uterus betroffenen Frauen weisen zum Zeitpunkt der Diagnosestellung Fernmetastasen oder befallene Lymphknoten auf. Eine Studie aus den USA hat am Beispiel von Patientinnen mit einem Karzinosarkom im Stadium I untersucht, inwieweit eine Lymphadenektomie, Chemotherapie und Radiotherapie das Überleben beeinflussen.
Journal of Clinical Gynecology and Obstetrics · 2021 · 0 citations
A Rare Case of Transformation of Endometrial Carcinoma Into Uterine Carcinosarcoma
AbstractUterine carcinosarcoma (previously called malignant mixed Mullerian tumor) is a rare and aggressive cancer that is considered a high-risk variant of endometrial adenocarcinoma because of the resemblance in risk factors and clinical presentation with endometrial carcinoma. In the United States, the incidence of carcinosarcoma is approximately 1 to 4 per 100,000 women. The clinical features, diagnosis, staging, and treatment of uterine carcinosarcoma will be discussed in this topic review. To our knowledge, this is one of the few reported cases of endometrial carcinoma that has transformed into uterine carcinosarcoma. J Clin Gynecol Obstet. 2021;10(3):81-85 doi: https://doi.org/10.14740/jcgo677
Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition
AbstractUterine carcinosarcoma is an aggressive variant of endometrial carcinoma characterized by unusual histologic features including discrete malignant epithelial and mesenchymal components (carcinoma and sarcoma). Recent studies have confirmed a monoclonal origin, and comprehensive genomic characterizations have identified mutations such as <em>Tp53</em> and <em>Pten</em> However, the biological origins and specific combination of driver events underpinning uterine carcinosarcoma have remained mysterious. Here, we explored the role of the tumor suppressor <em>Fbxw7</em> in endometrial cancer through defined genetic model systems. Inactivation of <em>Fbxw7</em> and <em>Pten</em> resulted in the formation of precancerous lesions (endometrioid intraepithelial neoplasia) and well-differentiated endometrioid adenocarcinomas. Surprisingly, all adenocarcinomas eventually developed into definitive uterine carcinosarcomas with carcinomatous and sarcomatous elements including heterologous differentiation, yielding a faithful genetically engineered model of this cancer type. Genomic analysis showed that most tumors spontaneously acquired <em>Trp53</em> mutations, pointing to a triad of pathways (p53, PI3K, and Fbxw7) as the critical combination underpinning uterine carcinosarcoma, and to Fbxw7 as a key driver of this enigmatic endometrial cancer type. Lineage tracing provided formal genetic proof that the uterine carcinosarcoma cell of origin is an endometrial epithelial cell that subsequently undergoes a prominent epithelial-mesenchymal transition underlying the attainment of a highly invasive phenotype specifically driven by Fbxw7.
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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