DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for endometrium adenocarcinoma — 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 moduleEndometrium adenocarcinoma 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
No approved-drug candidate for endometrium adenocarcinoma 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
Endometrial adenocarcinoma is the most common malignancy of the female genital tract in the United States, and although many clinicians view it as relatively benign due to early symptoms and generally high survival rates, the estimated number of deaths continues to increase. Molecular analysis from 1995 identified HER-2/neu overexpression in 10% of endometrial cancers, correlating with poor survival, while K-ras mutations occur in 10% of American and 20-30% of Japanese cases, and p53 mutations in 20% of endometrial adenocarcinomas, also associated with advanced stage and poor survival. Microsatellite instability has been observed in some endometrial cancers, but the molecular pathogenesis remains poorly understood. A 2024 review summarises progress on small molecule targeted therapies directed at PI3K/Akt/mTOR, PARP, GSK-3β, STAT-3, and VEGF pathways, but provides no efficacy data from clinical trials, and notes that adjuvant chemotherapy faces drawbacks including drug resistance.
A 1966 case report describes adenocarcinoma developing in both endometrial and adenomyotic epithelium, concluding that malignant transformation occurred in a susceptible field including both tissues, with rare examples of carcinoma confined solely to adenomyosis representing limit cases; the possible effect of estrogen is reviewed. A 1984 German-language case report of a septate uterus with adenocarcinoma in one horn concludes there is no causal link between uterine malformation and carcinoma, only coincidence, though unrecognised malformations can delay diagnosis and disrupt therapy. A 2015 comprehensive review confirms that despite most patients presenting with early-stage disease, metastatic disease is recognised in a substantial proportion when comprehensive surgical staging is performed, and FIGO has recommended total hysterectomy, bilateral salpingo-oophorectomy, peritoneal cytology, and lymph node dissection since 1988.
A 2018 review of adenomyosis notes it is asymptomatic in one-third of cases, affects up to 50% of women with infertility, and is a risk factor for spontaneous pre-term delivery and pre-term premature rupture of membranes, but its etiology remains unclear. A 2023 review discusses cancer-associated gene mutations detected in endometriosis, adenomyosis, and normal endometrium, suggesting accumulation of genomic alterations is a critical carcinogenic mechanism in progression from normal endometrium to ovarian clear cell carcinoma via endometriosis, but does not establish a direct pathway for endometrial adenocarcinoma. No abstract in this set reports a successful therapeutic intervention, a survival benefit from any drug, or a completed trial in endometrial adenocarcinoma; the 2024 targeted therapy review is speculative and calls for further understanding rather than presenting results.
What is missing is any clinical trial evidence for repurposed drugs in this disease, a coherent molecular stratification linking the identified mutations (p53, K-ras, HER-2/neu) to specific treatment responses, and prospective data on whether adenomyosis or normal endometrial genomic alterations can predict malignant progression. Funding for prospective biomarker-driven trials and standardised imaging criteria for adenomyosis would be needed before any drug could be evaluated meaningfully.
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 · 1995 · 104 citations · open access
Molecular basis of endometrial cancer
AbstractBACKGROUND: Most human cancers are thought to arise from alterations in oncogenes and tumor suppressor genes. METHODS: Molecular techniques have been used to identify specific genetic alterations in endometrial cancers. RESULTS: Overexpression of the HER-2/neu oncogene occurs in 10% of endometrial cancers and correlates with poor survival. Alterations in other receptor tyrosine kinases (c-fms and epidermal growth factor receptor) also occur in some cases. The c-myc oncogene, which encodes a nuclear transcription factor, also may be overexpressed in some invasive cancers. Mutations in the K-ras oncogene occur in 10% and in 20-30% of American and Japanese endometrial cancers, respectively. K-ras mutations also have been observed in endometrial hyperplasias, and this may represent an early event in the development of some cancers. Mutation of the p53 tumor suppressor gene, with resultant overexpression of mutant p53 protein, occurs in 20% of endometrial adenocarcinomas. Overexpression of p53 is associated with advanced stage and poor survival. Because p53 mutations do not occur frequently in endometrial hyperplasias, this may be a relatively late event in endometrial carcinogenesis. Recent studies have shown that mutations occur in microsatellite sequences in some endometrial cancers. Because microsatellite instability in hereditary nonpolyposis colon cancer has been found to be caused by mutations in DNA repair genes, similar mutations are being sought in endometrial cancers. CONCLUSIONS: Although several molecular alterations have been identified, the molecular pathogenesis of endometrial cancer remains poorly understood.
Advances in Clinical and Experimental Medicine · 2018 · 29 citations · open access
Current facts constituting an understandingof the nature of adenomyosis
AbstractAdenomyosis seems to be the most widespread coexistent pathology included under the umbrella of common benign disorders of the human uterus. The incidence of adenomyosis is under discussion since different imaging criteria are used. In the majority of cases, prevalence is determined among women with uterine fibroids and endometriosis or severe gynecological symptoms. This common benign pathology is asymptomatic in 1/3 of cases. Up to 50% of women with infertility are affected by adenomyosis. It seems to be an important risk factor for spontaneous pre-term delivery and pre-term premature rupture of the membranes. Nowadays, the etiology of adenomyosis is still unclear and requires deeper investigation. This review summarizes the aspects of prevalence, co-existence, risk factors, classification, mechanisms of pathogenesis, genes and immunological features, main histological features, animal models, and clinical manifestation of adenomyosis. It might facilitate understanding of the independent nature of such a dual enigma as adenomyosis.
Adenocarcinoma of endometrium involving adenomyosis. Report of an unusual case and review of the literature
AbstractA case of adenocarcinoma developing in endometrial and adenomyotic epithelium is presented. The pattern of development of the carcinoma is discussed in relation to the histogenesis of adenomyosis. The authors conclude that the malignant transformation occurred in a susceptible field that included both endometrial and adenomyotic epithelium. The rare examples of adenocarcinoma arising in and confined solely to adenomyosis represent limit cases. The possible effect of estrogen is reviewed.
Journal of the National Comprehensive Cancer Network · 2006 · 14 citations
Uterine Cancers Clinical Practice Guidelines
AbstractAdenocarcinoma of the endometrium is the most common malignancy of the female genital tract in the United States. Many physicians believe that adenocarcinoma of the endometrium is a relatively benign disease because of the early symptoms of irregular vaginal bleeding in this predominantly postmenopausal patient population, the often-localized nature of the disease, and the generally high survival rate. However, the estimated number of deaths from endometrial cancer continues to increase, indicating the need for a critical reassessment of the guidelines for managing endometrial cancer. Physicians must identify high-risk patients and tailor treatment appropriately to provide the best opportunity for long-term survival. For the most recent version of the guidelines, please visit NCCN.org
Small molecule targeted therapies for endometrial cancer: progress, challenges, and opportunities
AbstractEndometrial cancer (EC) is a common malignancy among women worldwide, and its recurrence makes it a common cause of cancer-related death. Surgery and external radiation, chemotherapy, or a combination of strategies are the cornerstone of therapy for EC patients. However, adjuvant treatment strategies face certain drawbacks, such as resistance to chemotherapeutic drugs; therefore, it is imperative to explore innovative therapeutic strategies to improve the prognosis of EC. With the development of pathology and pathophysiology, several biological targets associated with EC have been identified, including PI3K/Akt/mTOR, PARP, GSK-3β, STAT-3, and VEGF. In this review, we summarize the progress of small molecule targeted therapies in terms of both basic research and clinical trials and provide cases of small molecules combined with fluorescence properties in the clinical applications of integrated diagnosis and treatment. We hope that this review will facilitate the further understanding of the regulatory mechanism governing the dysregulation of oncogenic signaling in EC and provide insights into the possible future directions of targeted therapeutic regimens for EC treatment by developing new agents with fluorescence properties for the clinical applications of integrated diagnosis and treatment.
Journal of obstetrics and gynaecology research · 2023 · 1 citations
Pathogenesis of endometrium‐related diseases based on genomic alterations in normal uterine endometrium
AbstractThe human endometrium is a dynamically remodeling tissue that undergoes more than 400 cycles of regeneration, differentiation, shedding, and rapid healing during a woman's reproductive years. The endometrium is also the origin of various gynecologic diseases, such as endometriosis, adenomyosis, and uterine corpus cancer. Cancer-associated gene mutations are detected in endometriosis, adenomyosis, and normal endometrium. Some reports have demonstrated that the accumulation of genomic alterations is a critical carcinogenic mechanism in the progression from normal endometrium to ovarian clear cell carcinoma via endometriosis. In this review, we discuss the clinical importance of genomic alterations in the normal endometrium, contributing to the elucidation of the pathogenesis of endometrium-related diseases.
Geburtshilfe und Frauenheilkunde · 1984 · 1 citations
Uterus septus mit Adenokarzinom der einen Korpushälfte
AbstractEs wird der seltene Fall der Kombination eines Uterus septus mit einem auf einen Uterusanteil beschränkten reifzelligen Adenokarzinom des Endometriums dargestellt. Bei dem gleichzeitigen Auftreten von Uterusdoppelmißbildung und Karzinom besteht kein ursächlicher Zusammenhang, sondern bloße Koinzidenz. Nicht erkannte Uterusmißbildungen können zu schwerwiegender Verzögerung der Diagnose eines Karzinoms des Organes sowie auch zur Störung therapeutischer Bemühungen führen.
Past, Present and Future Perspectives on the Management of Endometrial Cancer— A Comprehensive Review
AbstractDespite the vast majority of patients diagnosed with endometrial cancer present to clinical attention with early stage disease limited to uterus, metastatic disease is recognized in a substantial proportion when comprehensive surgical staging is carried out In 1988, the International Federation of Gynecologists and Obstetricians (FIGO) officially suggested surgical staging as part of the primary management plan for endometrial cancer. Despite the recent amendments of the staging system in 2009, comprehensive staging (total hysterectomy, bilateral salpingooophorectomy, peritoneal cytology, intraoperative bilateral pelvic and paraaortic lymph node dissection) continue to be recommended
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, resolved on OpenAlex.
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