DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for breast ductal carcinoma in situ — screening already-approved drugs against its 37-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBreast ductal carcinoma in situ maps to a 37-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 breast ductal carcinoma in situ 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
HRas proto-oncogene, GTPase (HRAS) — HRAS 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ELT · 1.66 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
Ductal carcinoma in situ accounts for a majority of noninvasive breast cancer cases and constitutes 15% to 30% of all newly diagnosed breast cancers. There is little known about the molecular etiology behind each DCIS lesion or grade, and the progression to invasive ductal carcinoma is not well understood. DCIS lesions are heterogeneous in morphology, genetics, cellular biology, and clinical behaviour, and approximately half of all DCIS lesions progress to an invasive status. There remains great controversy regarding screening, diagnosis, and treatment.
A 2019 and 2020 epithelial cell-based study analysed archival formalin-fixed paraffin-embedded blocks from six patients with pure invasive ductal carcinoma, six with pure DCIS, six with synchronous invasive ductal carcinoma with an in-situ component, and three non-neoplastic breast epithelium tissues. Gene expression profiling of 770 genes showed that pure DCIS had one of the most altered gene expression profiles compared with non-neoplastic tissue. Comparing pure DCIS and the in-situ component, six differentially expressed genes were found, three of which — FGF2, GAS1, and SFRP1 — play a role in cell invasiveness. These three genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis. The authors proposed these three genes as potential biomarkers of DCIS progression, suggesting their downregulation may be involved in the transition from stationary to migrating invasive epithelial cells.
No drug was tested in any of these studies. The 2016 Chinese expert consensus acknowledged ongoing disagreement over screening, diagnosis, and treatment of breast carcinoma in situ, and the 2022 review stated that new strategies pinpointing molecular mechanisms are necessary to overcome the gap in understanding that is a barrier to more targeted therapy. The biomarker study involved only six patients per group, a very small sample that limits any generalisable conclusion.
What is still missing is large-scale, prospective validation of the proposed biomarkers in diverse patient populations, funding for adequately powered studies that can stratify DCIS by molecular risk, and clinical trials that test whether biomarker-guided management reduces both overtreatment and undertreatment. No drug repurposing candidate has been identified or tested in these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Endocrinology · 2022 · 30 citations · open access
Ductal Carcinoma In Situ of Breast: From Molecular Etiology to Therapeutic Management
AbstractDuctal carcinoma in situ (DCIS) makes up a majority of noninvasive breast cancer cases. DCIS is a neoplastic proliferation of epithelial cells within the ductal structure of the breast. Currently, there is little known about the progression of DCIS to invasive ductal carcinoma (IDC), or the molecular etiology behind each DCIS lesion or grade. The DCIS lesions can be heterogeneous in morphology, genetics, cellular biology, and clinical behavior, posing challenges to our understanding of the molecular mechanisms by which approximately half of all DCIS lesions progress to an invasive status. New strategies that pinpoint molecular mechanisms are necessary to overcome this gap in understanding, which is a barrier to more targeted therapy. In this review, we will discuss the etiological factors associated with DCIS, as well as the complexity of each nuclear grade lesion. Moreover, we will discuss the possible molecular features that lead to progression of DCIS to IDC. We will highlight current therapeutic management and areas for improvement.
[Chinese expert consensus on the diagnosis and treatment of breast carcinoma in situ].
AbstractIn situ carcinomas of the breast constitute 15% to 30% of all newly diagnosed breast cancer cases. Although the concept of carcinoma in situ has been proposed for a long time, there is still a great controversy regarding the screening, diagnosis and treatment. This article attempts to reach some consensus on the management of ductal carcinoma in situ and lobular carcinoma in situ and provide references for clinicians in the following aspects: definition and classification, natural history and prognosis, diagnosis, local and systemic treatment for primary carcinoma in situ, recurrence risk and treatment approaches for recurrent cancers.
Research Square · 2019 · 0 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’s treatment. Our aim was to identify potentially 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.
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.
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.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
