DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for collecting duct carcinoma — 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 moduleCollecting duct carcinoma 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
approvedSunitinibApproved drug
Structures already discussed alongside collecting duct carcinoma 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
The 2006 Japanese nationwide survey identified 81 confirmed cases of collecting duct carcinoma from 120 submitted. Mean age was 58.2 years, 71.6% were male, 65.4% presented symptomatically, and 32.1% had distant metastases at diagnosis. Among patients who had lymph node dissection, 44.2% had histologically confirmed nodal involvement. Postoperative adjuvant therapy was given to 25 patients; only one showed a partial response, to combined gemcitabine and carboplatin for lung metastases. At a median follow-up of 15 months, disease-specific survival was 69.0% at one year, 45.3% at three years, 34.3% at five years, and 13.7% at ten years. The authors concluded that advanced or recurrent collecting duct carcinoma is resistant to standard treatments.
The remaining abstracts concern ductal carcinoma in situ of the breast, a different disease. One 2024 review states that ductal carcinoma in situ has a 10-year breast cancer-specific survival of 97–98% with current treatment, and that some patients with low-grade disease may not require surgery. A 2015 review found that patients with ductal carcinoma in situ often experience decisional conflict, anxiety, and confusion due to conflicting expert messages and lack of knowledge. Two 2020 studies examined biomarkers: one identified low NMI expression in 49.7% of invasive ductal carcinomas, associated with triple-negative subtype and poorer progression-free survival; the other proposed FGF2, GAS1, and SFRP1 as potential biomarkers of progression from ductal carcinoma in situ to invasive disease, noting their downregulation in later stages.
No abstract in this set reports a prospective trial of any drug for collecting duct carcinoma. The only hint of a response was a single patient in a retrospective survey. What is missing is any dedicated clinical trial, any validated biomarker to select patients, and any funding for a disease so rare that even a nationwide survey could only gather 81 confirmed cases over two years.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Urology · 2006 · 188 citations
Collecting Duct (Bellini Duct) Renal Cell Carcinoma: A Nationwide Survey in Japan
AbstractPURPOSE: Collecting duct carcinoma, a rare type of renal cell carcinoma, remains poorly understood. To analyze the nature of collecting duct carcinoma a retrospective survey was performed in Japan. MATERIALS AND METHODS: This survey was done from August 2001 to April 2003. A total of 281 institutions throughout Japan were requested to document all cases of collecting duct carcinoma. All pertinent clinical information was compiled, including patient age, sex, mode of presentation, evaluation modality, preoperative laboratory data, surgery type, macroscopic and microscopic findings, and survival data. Two urological pathologists reviewed microscopic slides of all tumor specimens to confirm collecting duct carcinoma. RESULTS: Two pathologists confirmed collecting duct carcinoma in 81 of the 120 cases documented as collecting duct carcinoma. Mean patient age was 58.2 years and males comprised 71.6% of all patients. The mode of presentation was classified as symptomatic in 65.4% of cases, incidental in 24.7% and not available in 9.9%. Regional lymph node metastasis was histologically detected in 44.2% of patients who underwent lymph node dissection, while 32.1% of the population had distant metastasis at presentation. Although postoperative adjuvant therapy against metastasis or recurrence was performed in 25 patients, no obvious responses were identified except in 1 with lung metastases, who showed a partial response to combined gemcitabine and carboplatin therapy. At a median followup of 15 months 1, 3, 5 and 10-year disease specific survival was 69.0%, 45.3%, 34.3% and 13.7%, respectively. CONCLUSIONS: We report what is to our knowledge the largest known series of collecting duct carcinoma. Since advanced or recurrent collecting duct carcinoma is resistant to standard treatment modalities, new treatment strategies are needed for advanced collecting duct carcinoma.
Current Opinion in Obstetrics & Gynecology · 2007 · 22 citations
Ductal carcinoma in situ: a review of recent advances
AbstractPURPOSE OF REVIEW: This review summarizes recent findings on ductal carcinoma in situ of the breast and their impact on prognosis and management of the disease. RECENT FINDINGS: Great advances have been made in our understanding of ductal carcinoma in situ. Nuclear grading is probably the most important pathological factor that affects clinical outcome and correlates with distinct genetic pathways. Identifying key molecules in each pathway may provide better markers for prognostic, predictive and therapeutic purposes. Not all cases of ductal carcinoma in situ will progress to invasive ductal carcinoma, and identifying this subgroup of patients should lead to a reduction of overtreatment. Progenitor cell theory at the cellular level and sick lobe theory at the architectural level may help provide a better understanding of ductal carcinoma in situ from a different perspective and facilitate the development of individualized therapy. Prevention of local recurrence is the primary goal for treatment. Debate continues, however, on the use of radiotherapy, hormonal therapy, and sentinel lymph node biopsy. A panel of molecular markers may be needed for accurately predicting clinical outcome for the disease. SUMMARY: Understanding the carcinogenesis of ductal carcinoma in situ at the molecular level may lead to an optimal individualized therapy with minimal over or undertreatment.
Sunitinib in metastatic renal cell carcimoma: A single-center experience
AbstractINTRODUCTION: Historically, metastatic renal cell carcinoma (RCC) has had poor prognosis; the outcomes have improved with the introduction of tyrosine-kinase inhibitors, such as sunitinib. There is no reported literature from India on the use of sunitinib in metastatic RCC. We present an analysis of sunitinib at our institute over 4 years. MATERIALS AND METHODS: An unselected population of patients with metastatic or relapsed metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. RESULTS: Fifty-nine patients (51 males, 8 females) with a median age of 55 years were included in the study. Lungs and bones were the most common site of metastases. The patients received a median number of 4 cycles, with 23 patients requiring dose-modification and 12 discontinuing therapy due to toxicity. Overall, 38 patients (65%) had CR, PR, or standard deviation while 14 had progression or death at initial evaluation. The median progression-free survival (PFS) was 11.4 months and overall survival was 22.6 months. Hand-foot syndrome, fatigue, mucositis, skin rash, and vomiting were seen more often among our patients, whereas hypertension was not as common compared with previously published reports. CONCLUSION: Sunitinib is a viable option for the treatment of metastatic RCC and shows a comparable PFS in Indian patients. Although toxicity remains a concern, most of the adverse effects can be managed conservatively. Careful patient selection, tailoring the dose of therapy, adequate counseling, and careful follow-up is essential for optimum therapy.
Japanese Journal of Clinical Oncology · 2024 · 10 citations · open access
Update on the management of ductal carcinoma <i>in situ</i> of the breast: current approach and future perspectives
AbstractThe standard treatment for ductal carcinoma in situ became well established through the results of several valuable clinical trials, and its therapeutic benefits have now come to be taken for granted. Ductal carcinoma in situ has an extremely good prognosis with the current treatment approach, with a 10-year breast cancer-specific survival rate of 97-98%. According to one retrospective cohort study, the breast cancer-specific survival rate of patients with low-grade ductal carcinoma in situ does not differ significantly between patients undergoing and not undergoing surgery. Some patients with ductal carcinoma in situ are not at a risk of progression to invasive cancer, but the predictors of such progression have not yet been clearly identified. Therefore, the same therapeutic strategies have been used to treat ductal carcinoma in situ and under the assumption that they have risks of invasive breast cancer, and a well-balanced risk/benefit ratio in respect of treatment has not yet been achieved. Based on the results of several recent clinical trials aimed at ensuring provision of a well-balanced treatment for patients with ductal carcinoma in situ which carries a good prognosis, de-escalation of postoperative adjuvant therapy has now begun. Currently, not only is the optimization of postoperative adjuvant therapy accelerating, but also clinical trials to de-escalate basic surgical treatments are under way. There is a possibility of achieving individualized treatment for patients with ductal carcinoma in situ of the breast with reduced treatment intervention. In this review, we present an overview of the current treatment approaches and potential future management strategies for ductal carcinoma in situ of the breast.
Anticancer Research · 2021 · 6 citations · open access
Adenosine Induces Autophagy in Cholangiocarcinoma Cells
AbstractBACKGROUND/AIM: Cholangiocarcinoma is a lethal disease with increasing incidence worldwide. New therapeutic compounds are urgently needed for this disease. Here, the inhibitory effect of adenosine on cholangiocarcinoma cells was studied. MATERIALS AND METHODS: Western blot analysis was used to study autophagy and flow cytometry to analyze cell death and the cell cycle. RESULTS: Cholangiocarcinoma and immortalized cholangiocytes responded to adenosine differently, and adenosine inhibited cholangiocarcinoma cell growth by inducing autophagy. Adenosine failed to activate adenylyl cyclase in cholangiocarcinoma cell lines, but activated this enzyme in immortalized cholangiocytes. Adenosine treatment activated AMPK and led to phosphorylation of its downstream proteins including ULK and Raptor. In addition, autophagy induced by adenosine appeared to be a survival mechanism. The combination of adenosine with autophagy inhibitors greatly increased cell death, as compared to the use of either agent alone. Interestingly, immortalized cholangiocytes were more resistant to adenosine. CONCLUSION: Adenosine may have potential for application in cholangiocarcinoma treatment.
Journal of Breast Cancer · 2020 · 1 citations · open access
Downregulation of N-myc and STAT Interactor Protein Predicts Aggressive Tumor Behavior and Poor Prognosis in Invasive Ductal Carcinoma
AbstractWe investigated the expression of the N-myc and STAT interactor (NMI) protein in invasive ductal carcinoma tissue and estimated its clinicopathologic significance as a prognostic factor. The expression levels and prognostic significance of NMI were also analyzed according to the molecular subgroup of breast cancers. Methods: Human NMI detection by immunohistochemistry was performed using tissue microarrays of 382 invasive ductal carcinomas. The correlation of NMI expression with patient clinicopathological parameters and prognostic significance was analyzed and further assessed according to the molecular subgroup of breast cancers. Moreover, in vitro experiments with 13 breast cancer cell lines were carried out. We also validated NMI expression significance in The Cancer Genome Atlas cohort using the Human Protein Atlas (HPA) database. Results: Low NMI expression was observed in 190 cases (49.7%). Low NMI expression was significantly associated with the "triple-negative" molecular subtype (p < 0.001), high nuclear grade (p < 0.001), high histologic grade (p < 0.001), and advanced anatomic stage (p = 0.041). Patients with low NMI expression had poorer progression-free survival (p = 0.038) than patients with high NMI expression. Low NMI expression was not significantly associated with patient prognosis in the molecular subgroup analysis. In vitro, a reduction of NMI expression was observed in 8 breast cancer cell lines, especially in the estrogen receptor-positive and basal B type of triple-negative breast cancer molecular subgroups. The HPA database showed that low NMI expression levels were associated with a lower survival probability compared with that associated with high NMI expression (p = 0.053). Conclusion: NMI expression could be a useful prognostic biomarker and a potential novel therapeutic target in invasive ductal carcinoma.
Research Square · 2020 · 1 citations · open access
Potential biomarkers of ductal carcinoma in situ progression
AbstractAbstract Background Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk.Methods In this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ) , six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies. Results The results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them ( FGF2 , GAS1, and SFRP1 ), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis. Conclusions We propose these three genes ( FGF2 , GAS1, and SFRP1 ) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.
Journal of patient-centered research and reviews · 2015 · 0 citations · open access
Ductal Carcinoma in Situ Treatment Decision-Making and Patient-Reported Outcomes: A Review of the Literature
AbstractBackground/Aims: The treatment for ductal carcinoma in situ (DCIS) is similar to invasive breast cancer despite evidence of low 10-year recurrence rates and mortality. Patient preferences and involvement with decision-making should play a key role in treatment decisions; however, little are known about how decision-making about the type of treatment influences patient-reported outcomes. The objective is to review the recent literature to determine how decision-making for treatment of DCIS influences patient-reported outcomes and to make recommendations on future studies to improve decision-making practices. Methods: A search of PubMed database was conducted for manuscripts published 2009–2014. Search terms included “ductal carcinoma in situ” and “satisfaction with treatment” (n=33), “decisional conflict” (n=1) or “patient decision making” (n=137). Only articles that included patient-reported decision-making were included in the review. Articles were excluded if they aggregated patients with invasive or metastatic breast cancer. Results: There were a total of 11 articles included in the review. We found that decisional conflict among patients was common. Physicians play an important role in women understanding the disease; however, there is controversy about treatment of DCIS among experts. Decisional conflict was related to a lack of knowledge about the disease, which led to confusion, anxiety, fear and depression. The studies showed that conflicting messages from health care professionals negatively impacted patient’s abilities to make informed treatment decisions and patient-reported outcomes. In terms of health disparities, one study found that a lack of understanding about DCIS was greater in women from non-English speaking backgrounds. Recommendations for future research include: 1) improve knowledge of DCIS and its complexities among health care professionals and patients, 2) address knowledge gaps by developing and testing the efficacy of “decision aids” to improve patients comfort in making informed treatment choices, 3) evaluate why various messages about DCIS exist among health care professionals, and 4) address the need to establish consensus on guidelines. Discussion: The literature suggests that patients often have a lack of knowledge and experience adverse psychological outcomes associated with a diagnosis of DCIS. More research is needed to improve informed treatment decisions about the disease for patients diagnosed with DCIS.
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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