DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for ovarian mucinous adenocarcinoma — screening already-approved drugs against its 49-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleOvarian mucinous adenocarcinoma maps to a 49-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 ovarian mucinous 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
Bruton tyrosine kinase (BTK) — BTK 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 7h-pyrrolo[2,3-d]pyrimidin-4-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6VXQ · 1.4 Å · ligand N-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl}benzamide (RQS). Experimental structure, not a prediction.
What the evidence adds up to
Mucinous ovarian cancer accounts for roughly 3% of all epithelial ovarian cancers and is now recognised as a distinct entity from the more common serous subtype, though it is still often treated with the same chemotherapy protocols. Early-stage disease carries an excellent prognosis, while advanced disease has a poor outcome. In a retrospective analysis of 45 patients with stage I/II mucinous ovarian cancer, the 3-year progression-free survival was 96% and the 5-year PFS was 91%, compared to 82.4% and 75.1% respectively in non-mucinous patients. Among these early-stage mucinous patients, 35.6% underwent fertility-sparing surgery and none experienced recurrence; systematic lymphadenectomy did not significantly affect recurrence rates and the authors suggest it may be omitted. 68.8% of these patients received adjuvant chemotherapy.
One case report describes a 45-year-old pregnant woman with a large ovarian mucinous adenocarcinoma treated with surgical resection and adjuvant carboplatin plus paclitaxel; she remained in complete remission at 36 months of follow-up. The rarity of the diagnosis during pregnancy means management remains poorly codified. No prospective trial data exist to guide chemotherapy choice specifically for mucinous ovarian cancer, and gastrointestinal regimens have sometimes been used alongside standard gynaecological protocols.
Molecular profiling of a rare dedifferentiated mucinous ovarian carcinoma identified mutations in TP53 and KRAS, which are already known in this tumour type, and also in CEP170, a gene involved in microtubule dynamics. CEP170 mutations were found in 33.3% of dedifferentiated mucinous carcinoma samples tested. The functional relevance of CEP170 in carcinogenesis is still under investigation. What remains missing is a dedicated prospective trial for mucinous ovarian cancer, which would require multicentre collaboration given its low incidence, and adequate funding to test targeted therapies based on the molecular alterations now being catalogued. Patient stratification by stage, differentiation status, and mutational profile is not yet standardised.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Diagnostics · 2020 · 133 citations · open access
Mucinous Cancer of the Ovary: Overview and Current Status
AbstractMucinous ovarian cancer (MOC) is a rare subtype of epithelial ovarian carcinoma (EOC). Whereas all EOC subtypes are addressed in the same way, MOC is a distinct entity. Appreciating the pathological features and genomic profile of MOC may result in the improvement in management and, hence, the prognosis. Distinguishing primary MOC from metastatic mucinous carcinoma can be challenging but is essential. Early-stage MOC carries an excellent prognosis, with advanced disease having a poor outcome. Surgical management plays an essential role in the early stage and in metastatic disease. Chemotherapy is usually administered for stage II MOC and beyond. The standard gynecology protocol is frequently used, but gastrointestinal regimens have also been administered. As MOC is associated with multiple molecular alterations, targeted therapy could be the answer to treat this disease.
International Journal of Molecular Sciences · 2018 · 67 citations · open access
Recent Insights into Mucinous Ovarian Carcinoma
AbstractOvarian mucinous tumors represent a group of rare neoplasms with a still undefined cell of origin but with an apparent progression from benign to borderline to carcinoma. Even though these tumors are different from the other histological subtypes of epithelial ovarian neoplasms, they are still treated with a similar chemotherapeutic approach. Here, we review its pathogenesis, molecular alterations, (differential) diagnosis, clinical presentation and current treatment, and how recent molecular and biological information on this tumor might lead to better and more specific clinical management of patients with mucinous ovarian carcinoma.
Abstract(Abstracted from N Engl J Med 2019;380:1256–1266) Mucinous ovarian cancer is a rare form of epithelial ovarian cancer, accounting for approximately 3% of all cases. New understanding of the biological features of this unique disease requires an update to traditional diagnostic and therapeutic protocols that have been historically based on guidelines for serous ovarian carcinoma.
International Journal of Surgery Case Reports · 2022 · 6 citations · open access
Bilateral ovarian mucinous carcinoma (stage III) with omental involvement and incidental hydronephrosis
AbstractINTRODUCTION: Though ovarian malignancies are common, mucinous ovarian carcinomas of high grade are rare. They usually occur in a young female under 40 years of age. Here, we present a case of mucinous ovarian carcinoma (stage III), with omental involvement and incidental hydronephrosis in a 67-year-old female patient. CASE PRESENTATION: A 67-year-old female patient presented to us with a history of lower abdominal pain for 2 months and per-vaginal discharge for the last 6 days. On deep palpation of the abdomen, a nodular mass occupying the suprapubic region was found. Bimanual palpation revealed a mass on the right and left adnexa. After visualization of septate cystic mass bilaterally on CECT, she was planned for staging laparotomy with bilateral salpingo-oophorectomy (BSO) with infra-colic omentectomy with peritoneal cytology. Incidentally, a horseshoe-shaped kidney with right mild hydronephrosis was found. After surgery and histopathologic examination, mucinous ovarian carcinoma (stage III), with omental involvement was confirmed. DISCUSSION: Mucinous ovarian carcinomas are rare malignancies, with different natural history, molecular profile, and prognosis as compared to other epithelial tumors of the ovary. These carcinomas can be either primary or secondary (those metastasized to the ovary from elsewhere), and this differentiation is essential. The therapeutic approach to the patients depends upon the stage at which these carcinomas are diagnosed. CONCLUSION: Mucinous ovarian carcinomas are rare and have unique features among the epithelial ovarian carcinomas. Appreciation of these features will surely make a positive impact in improving the management and thus the prognosis of these carcinomas.
Journal of Cancer Science and Clinical Therapeutics · 2019 · 2 citations · open access
Retrospective Analysis of Early Stage Mucinous Ovarian Cancersystematic Lymphadenectomy May Be Omitted
AbstractPurpose: Mucinous ovarian cancer is a less common epithelial ovarian cancer. Mucinous early stage ovarian cancer (mEOC) seems less aggressive than other histologic types and require more conservative treatment. This analysis was conducted to explore the clinical outcome and appropriate treatment of mEOC. Methods: Data was extracted from patients with stage I/II ovarian cancer from 1999 to 2010 at our institution. Patients were classified into mucinous group (n=45) and non-mucinous groups (n=159). Clinical features and survival outcomes were compared between the two groups. Results: The 3-year/5-year progression free survival (PFS) of the mucinous were significantly longer than the non-mucinous group (96% /91.0% vs. 82.4% /75.1%, P=0.01). 40.0% of mEOC patients underwent systematic lymphadenectomy, and there was no significant differences of recurrence rate whether they received this procedure. 35.6% patients of mEOC underwent FSS and none of them experienced recurrence. 68.8% of mEOC patients received adjuvant chemotherapy. Conclusion: mEOC has longer PFS than other histologic types. Systematic lymphadenectomy may be omitted in mEOC patients.
Zenodo (CERN European Organization for Nuclear Research) · 2017 · 1 citations · open access
Screening Genetic Alterations of Biomarkers BRAF, ROS-1, and HER2 by Immunohistochemistry in Ovarian Carcinomas for Targeted Therapy
AbstractOvarian neoplasms are group of aggressive and lethal diseases. Surgical and radiochemical therapies on ovarian neoplasm are conventional approaches but with limited progress in years. Targeted therapy with drugs targeting specific genetic alterations and/or protein molecules have brought new hope fighting against ovarian neoplasms. Targeted therapy on genetic alterations of BRAF, ROS-1 and HER2 have been carried out in melanoma, lung cancer and breast cancer with promising results. However, knowledge of these genetic alterations in ovarian neoplasms is limited and deserves further exploration. In this study, we screened genetic alterations of BRAF, ROS-1 and HER2 by immunohistochemistry (IHC) on a variety of ovarian neoplasm, including 13 mucinous carcinomas, 12 clear cell carcinomas, 9 endometrioid carcinomas, 9 serous borderline tumors and 10 high grade serous tumor of fallopian tube. Although ROS-1 and HER2 abnormalities were not identified, BRAF V600E mutations were identified in 2 of 9 (22%) in borderline serous tumors. This finding has provided a knowledge base to further study the possibility of targeted therapy using BRAF inhibitor, such as vemurafeni, on borderline serous tumor of the ovary.
Annals of Medicine and Surgery · 2022 · 0 citations · open access
Rare association of the ovarian adenocarcinoma with pregnancy: A case report
AbstractThe association of ovarian malignancy with pregnancy is rare; accounting for 3-6% of ovarian masses of which malignant germ cell tumors represent the type most frequently associated with pregnancy, whereas the incidence of epithelial ovarian cancer is only 1/12,000 to 1/50,000 of pregnancies. The diagnosis and management of ovarian cancer in pregnancy remain poorly codified because of the rarity of cases and the limited data available on this pathology. We report here the case of a 45-year-old woman with a large ovarian mucinous adenocarcinoma diagnosed during pregnancy, identified by ultrasound and magnetic resonance imaging. The patient was treated by surgical resection followed by adjuvant chemotherapy with carboplatin and paclitaxel with a follow-up of 36 months, she is in complete remission.
Abstract 3383: Exome sequencing in dedifferentiated ovarian mucinous carcinoma
AbstractAbstract Mucinous ovarian tumor represent a distinct histotype of epithelial ovarian cancer and is thought to begin as a mucinous adenoma that progresses in a slow stepwise fashion. Dedifferentiated mucinous ovarian carcinoma is a rare type of carcinoma with a few reports and a progressive and poor prognosis. While the molecular genetic features of ovarian mucinous carcinoma is now well known, the pathogenesis of dedifferentiated mucinous carcinoma is largely unknown. In order to comprehensively analyse somatic mutations in dedifferentiated mucinous carcinoma, we applied exome sequencing to the DNA of a sample of affinity-purified, dedifferentiated mucinous carcinoma. Through comparative analyses of normal cells from the same patient, we identified several genes that were mutated in this tumor. P53, which encodes a well-known tumor suppressor protein, and KRAS, which encodes a well-known oncoprotein, had previously been implicated in ovarian mucinous carcinoma. The other mutated genes were previously unknown to be involved in mucinous carcinoma. CEP170 encodes a microtubule-binding protein that controls the targeting of the kinesin-13 depolymerase protein to the mitotic spindle, and kinesin-13 family influence the dynamics of microtubule growth and shrinkage. CEP170 gene mutation may be related to inability of a cell division properly. CEP170 mutations were identified with a prevalence of 33.3% in dedifferentiated mucinous ovarian carcinoma. Currently, CEP170 gene knock down assay and engineered expression of CEP170 assay in ovarian mucinous carcinoma is being performed whether morphologic change is observed. In summary, CEP170 may be one of the responsible gene in carcinogenesis of differentiated mucinous carcinoma. Citation Format: Kaori Sanuki, Kentaro Nakayama, Kohei Nakamura, Masako Ishikawa, Tomoka Ishibashi, Hitomi Yamashita, Ruriko Ono, Toshiko Minamoto, Kosuke Yoshihara, Satoru Kyo. Exome sequencing in dedifferentiated ovarian mucinous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3383. doi:10.1158/1538-7445.AM2017-3383
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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