DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for endometrial cancer — screening already-approved drugs against its 54-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEndometrial cancer maps to a 54-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
approvedSunitinibApproved drugapprovedPaclitaxelApproved drug
Structures already discussed alongside endometrial cancer 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
About 10% of endometrial cancers overexpress HER-2/neu, and that finding correlates with poor survival. K-ras mutations occur in 10% of American cases and 20–30% of Japanese cases; they also appear in endometrial hyperplasias, suggesting an early role in some cancers. p53 mutations are found in 20% of endometrial adenocarcinomas, are linked to advanced stage and poor survival, and seem to be a late event because they are rare in hyperplasias. Microsatellite instability has been observed, and DNA repair gene mutations are being investigated. Despite these identified alterations, the molecular pathogenesis of endometrial cancer was still described as poorly understood in 1995.
Recurrent or metastatic endometrial cancer is not curable. For women who progress after first-line treatment, options are limited. Carboplatin and paclitaxel are an acceptable alternative to cisplatin-based regimens. Radiation can be used for local or regional recurrence in patients who have not had prior radiotherapy; for those who have, pelvic exenteration may be an option. By 2013, clinical trials were evaluating angiogenesis inhibitors, mTOR inhibitors, and multitargeted tyrosine kinase inhibitors, but no novel agent had yet been proven to change the standard of care. A 2017 review noted that advanced disease still carries a grave prognosis and that novel therapies remain under investigation.
A 2024 review lists several biological targets under study in endometrial cancer: PI3K/Akt/mTOR, PARP, GSK-3β, STAT-3, and VEGF. It describes small molecule targeted therapies in both basic research and clinical trials, and mentions combining such agents with fluorescent properties for integrated diagnosis and treatment. Another 2024 paper discusses progestin-based pharmacotherapy for fertility preservation in early-stage disease, but provides no efficacy data. A large Japanese registry study covering 82,969 patients treated from 2012 to 2019 shows that chemotherapy alone or with hormonal therapy is more common in patients under 40 than in older women, and that laparoscopic or robot-assisted surgery has increased yearly. Small cell and undifferentiated carcinomas were more often diagnosed at an advanced stage.
What is still missing are completed, positive phase III trials that demonstrate a survival benefit for any targeted agent in recurrent endometrial cancer. Patient stratification by molecular subtype remains largely aspirational in routine practice. Funding for trials that enrol enough patients to detect meaningful differences in subgroups is inadequate, and no drug has yet been approved specifically for a molecularly defined endometrial cancer population outside of mismatch repair deficiency.
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.
American Journal of Clinical Oncology · 2013 · 85 citations
Advances in the Management of Recurrent Endometrial Cancer
AbstractOBJECTIVE: Endometrial carcinoma is the most common malignancy of the female reproductive tract. Although most cases are diagnosed at an early stage, endometrial carcinoma carries a poor prognosis when it recurs after previous definitive treatment or when diagnosed at an advanced stage. The purpose of this review is to summarize the contemporary management of recurrent endometrial carcinoma. METHODS: A literature review was conducted on the management of advanced, recurrent, or metastatic endometrial cancer to determine the best evidence to support the roles of surgery, radiation, and medical therapy. RESULTS: Radiation therapy (RT) has a role in the treatment of a local or regional recurrence, especially in the patient who has not had prior RT. For selected patients who experience a loco-regional recurrence and who have been treated with RT, pelvic exenteration may be an option. Those patients with metastatic disease are not curable and should be considered for palliative chemotherapy. The data support the use of carboplatin and paclitaxel as an acceptable alternative to cisplatin-based regimens. For women who progress after first-line treatment, the options are limited. Current clinical trials are evaluating the role of angiogenesis inhibitors and molecularly targeted therapy (including the mammalian target of rapamycin inhibitors and multitargeted tyrosine kinase inhibitors) with the aim of identifying other novel agents that can be exploited for treatment of advanced disease. CONCLUSIONS: The treatment of women with advanced, recurrent, or metastatic endometrial cancer represents an unmet need in oncology. Robust clinical trials are required to explore how to improve on therapy. The incorporation of molecularly targeted agents has the potential to improve outcomes for women who require treatment in both the first-line and second-line settings.
AbstractEndometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer.
Journal of Gynecologic Oncology · 2019 · 7 citations · open access
Sensitizing endometrial cancer to ionizing radiation by multi-tyrosine kinase inhibition
AbstractOBJECTIVE: Endometrial carcinoma is the most frequent gynecological cancer. About 15% of these cancers are of high risk and radiotherapy still remains the most suitable treatment. In this context, agents able to promote radiosensitization are of great interest. Here, we describe for the first time the radiosensitization ability of sunitinib in endometrial carcinoma. METHODS: Four endometrial carcinoma cell lines were used for the study. The activation of apoptosis signalling pathways and tyrosine kinase receptors were analysed by Western blot, luciferase assays and Immunoprecipitation. Radiosensitization effects were assessed using clonogenic assays. p65 and phosphatase and tensin homolog (PTEN) were upregulated by lentiviral transduction. RESULTS: We discovered that ionizing radiation activates the pro-oncogenic proteins and signalling pathways KIT, protein kinase B (AKT), and nuclear factor kappa B (NF-κB) and these activations were abrogated by sunitinib, resulting in a radiosensitization effect. We found out that AKT pathway is greatly involved in this process as PTEN restoration in the PTEN-deficient cell line RL95-2 is sufficient to inhibit AKT, rendering these cells more susceptible to ionizing radiation and sunitinib-induced radiosensitization. In Ishikawa 3-H-12 cells, radiosensitization effects and inhibition of AKT were achieved by PTEN restoration plus treatment with the phosphoinositide-3-kinase inhibitor LY294002. This suggests that endometrial tumors could have different sensitivity degree to radiotherapy and susceptibility to sunitinib-induced radiosensitization depending on their AKT activation levels. CONCLUSIONS: Our results provide the rationale of using sunitinib as neoadjuvant treatment prior radiotherapy which could be a starting point for the implementation of sunitinib and radiotherapy in the clinic for the treatment of recalcitrant endometrial cancers.
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.
Frontiers in Oncology · 2024 · 4 citations · open access
Progestin-based pharmacotherapy in fertility preservation in early endometrial cancer
AbstractEndometrial cancer is a common tumor of the female reproductive system. In recent years, as the age of onset of the disease has gradually become younger, this has caused distress to some young patients with reproductive needs, and the active search for methods of preserving reproductive function has gradually attracted attention. In this paper, we will systematize the current status of progestin-based pharmacotherapy in combination with other drug therapies in the conservative management of early-stage endometrial cancer. With the expectation of providing a reference for the treatment of early stage endometrial cancer patients in China and for the in-depth development of related research in this field.
Journal of Gynecologic Oncology · 2024 · 1 citations · open access
Detailed report on the clinicopathological factors of patients with endometrial cancer in Japan: a JSOG gynecologic tumor registry-based study
AbstractOBJECTIVE: In this study, we collected data over 8 years (2012-2019) from the Japan Society of Obstetrics and Gynecology (JSOG) tumor registry to determine the status of endometrial cancer in Japan, and analyzed detailed clinicopathological factors. METHODS: The JSOG maintains a tumor registry that gathers information on endometrial cancer treated at the JSOG-registered institutions. Data from the patients whose endometrial cancer treatment was initiated from 2012 to 2019 were analyzed retrospectively. RESULTS: A total of 82,969 patients with endometrial cancer underwent treatment from 2012 to 2019. Chemotherapy alone or in combination with hormonal therapy is more common among endometrial cancer patients under 40 years compared with those over 40 years. The number of patients with endometrial cancer, treated with laparoscopic or robot-assisted surgery was observed to have increased yearly. Small cell carcinomas and undifferentiated carcinomas were more likely to be diagnosed at an advanced stage. Lymphadenectomy was most commonly performed for stage IIIC2 disease, whereas positive peritoneal washing cytology was most common for stage IVB and serous carcinoma. CONCLUSION: Multi-year summary reports provided detailed clinicopathological information regarding endometrial cancer that could not be obtained in a single year. These reports were useful in understanding treatment strategies and trends over time based on age, histology, and stage.
AbstractThe patients with advanced (stage III, IV) endometrial cancer remain a substantial number with adverse prognostic features who relapse and die of this disease. Recently, the feasibility of administering the combination of chemotherapy and radiotherapy has been reported in the setting of advanced endometrial cancer with the impressive outcome. Sequential therapy consisted of paclitaxel and carboplatin for 3 cycles, followed by pelvic and/or para-aortic radiotherapy and an additional 3 cycles of chemotherapy, this ”sandwich” approach for patients with endometrial cancer has been studied recently. Several authors have reported that treatment modality is associated with a low rate of local recurrence and favorable survival for advanced endometrial cancer.
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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