DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for breast ductal adenocarcinoma — screening already-approved drugs against its 46-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 adenocarcinoma maps to a 46-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
Structures already discussed alongside breast ductal adenocarcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Structure of L1196M Mutant Anaplastic Lymphoma Kinase — Crizotinib has a real, experimentally solved structure in complex with this target (PDB 2YFX, 1.7 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 vghdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2YFX · 1.7 Å · ligand Crizotinib (VGH). Experimental structure, not a prediction.
What the evidence adds up to
Breast ductal adenocarcinoma is not a single disease. Microarray studies have focused almost exclusively on invasive ductal carcinomas of no special type, yet histological special types account for up to 25% of all invasive breast cancers and carry distinct genotypic-phenotypic correlations: secretory carcinomas harbour the ETV6-NTRK3 fusion gene, adenoid cystic carcinomas the MYB-NFIB translocation, and lobular carcinomas show inactivation of CDH1. The molecular taxonomy of breast cancer based on transcriptomic analysis has been proposed, but information conveyed by histological type has largely been ignored in these studies.
Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of epithelial cells within the ductal structure and makes up a majority of noninvasive breast cancer cases. Approximately half of all DCIS lesions progress to invasive ductal carcinoma, but the molecular mechanisms behind this progression remain poorly understood. DCIS lesions are heterogeneous in morphology, genetics, cellular biology, and clinical behaviour, and the pathophysiology of the disease is still poorly characterised despite many molecular studies aimed at identifying genes involved in breast cancer initiation and progression.
For DCIS, whole breast irradiation following breast-conserving surgery significantly reduces the risk of local relapse compared with surgery alone. Outcomes between breast-conserving surgery plus radiotherapy and mastectomy appear similar in the absence of extensive disease. A complementary boost to the surgical bed improves outcomes for invasive breast cancer, but its effect has never been prospectively reported for DCIS; two randomised controlled trials assessing this issue were still ongoing as of 2012. Risk factors for local relapse include young age, close or positive margins, and tumour necrosis.
A consensus has not been reached regarding the criteria to allow tumour excision alone for DCIS, and the extent of benefit of the main adjuvant therapies is becoming better established but remains debated. What is still missing is a prospective trial testing the radiotherapy boost specifically in DCIS, a molecular stratification that can predict which DCIS lesions will progress to invasion, and integration of histological special types into the molecular taxonomy so that rare but distinct entities are not overlooked in drug development.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Molecular Oncology · 2010 · 561 citations · open access
Histological types of breast cancer: How special are they?
AbstractBreast cancer is a heterogeneous disease, comprising multiple entities associated with distinctive histological and biological features, clinical presentations and behaviours and responses to therapy. Microarray-based technologies have unravelled the molecular underpinning of several characteristics of breast cancer, including metastatic propensity and histological grade, and have led to the identification of prognostic and predictive gene expression signatures. Furthermore, a molecular taxonomy of breast cancer based on transcriptomic analysis has been proposed. However, microarray studies have primarily focused on invasive ductal carcinomas of no special type. Owing to the relative rarity of special types of breast cancer, information about the biology and clinical behaviour of breast cancers conveyed by histological type has not been taken into account. Histological special types of breast cancer account for up to 25% of all invasive breast cancers. Recent studies have provided direct evidence of the existence of genotypic-phenotypic correlations. For instance, secretory carcinomas of the breast consistently harbour the t(12;15) translocation that leads to the formation of the ETV6-NTRK3 fusion gene, adenoid cystic carcinomas consistently display the t(6;9) MYB-NFIB translocation and lobular carcinomas consistently show inactivation of the CDH1 gene through multiple molecular mechanisms. Furthermore, histopathological and molecular analysis of tumours from conditional mouse models has provided direct evidence for the causative role of specific genes in the genesis of specific histological special types of breast cancer. Here we review the associations between the molecular taxonomy of breast cancer and histological special types, discuss the possible origins of the heterogeneity of breast cancer and propose an approach for the identification of novel therapeutic targets based on the study of histological special types of breast cancer.
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.
Molecular alterations in ductal carcinoma in situ of the breast
AbstractDespite recent improvements in the breast cancer mortality rate, breast cancer remains the most common cancer and the second leading cause of cancer-related deaths in US women. A decreasing trend in mortality rates is caused by advances in early detection and, to a lesser degree, in cancer therapies. With the increased utilization of mammography, one of the earliest detectable breast tumors, ductal carcinoma in situ, has become the most rapidly increasing subset of breast cancers. Contrary to the dramatic improvement in our ability to detect ductal carcinoma in situ, the pathophysiology of this disease is still poorly understood. Many molecular studies have been performed in ductal carcinoma in situ lesions with the aims of identifying genes involved in breast cancer initiation and progression, defining the relation between in situ and invasive carcinomas, and identifying clinically useful markers for breast cancer diagnosis, prognostication, prevention, and treatment.
International Journal of Surgical Oncology · 2012 · 9 citations · open access
Role of the Radiotherapy Boost on Local Control in Ductal Carcinoma<i>In Situ</i>
AbstractDuctal carcinoma in situ of the breast is associated with low mortality rates, but local relapse is a matter of concern in this disease. Risk factors for local relapse include young age, close or positive margins, and tumor necrosis. Whole breast irradiation following breast-conserving surgery for ductal carcinoma in situ significantly reduces the risk of local relapse as compared to breast-conserving surgery alone. Studies point to similar outcomes between breast-conserving surgery plus radiotherapy and mastectomy, in the absence of extensive disease. A complementary boost to the surgical bed improves outcomes for patients with invasive breast cancer. However, the effect of this strategy has never been prospectively reported for ductal carcinoma in situ. Two randomized controlled trials assessing this issue are ongoing. This paper represents an update on available literature about radiotherapy for DCIS with a special focus on the role of a radiotherapy boost to the tumor bed.
AbstractBACKGROUND: A large number of controversies about the management of breast cancer produce uncertainties for patients and physicians alike. In addition, questions are constantly raised about the true value of new approaches or treatments. METHODS: The authors have conducted a critical review of the literature on several of these issues, and they present a balanced view that can be useful for clinical decision making. RESULTS: Although new staging systems for ductal carcinoma in situ have been proposed, a consensus has not yet been reached regarding the criteria to allow tumor excision alone. The extent of benefit of the main adjuvant therapies is becoming better established, and improvement in outcomes may accrue from dose-intensive treatments and autologous stem cell or hematopoietic growth factor support. CONCLUSIONS: Progress in breast cancer management continues to evolve. Several new approaches either reduce morbidity or improve outcomes.
Sage Journals Data · 2019 · 0 citations · open access
ALK or ROS1-rearranged breast metastasis from lung adenocarcinoma: a report of 2 cases
AbstractBackground:Breast metastases from extramammary sites are extremely rare, with an incidence of 0.4%–1.3% reported in the literature. Insufficient knowledge about its pathology and genetic mutation often leads to misdiagnosis and delayed treatment.Case presentation:We present 2 patients with synchronous (case 1) or metachronous (case 2) breast nodules, revealed as atypical breast metastases from pulmonary adenocarcinomas, in which ALK or ROS1 rearrangement were finally detected in breast mass. After they failed sequential treatments with standard chemotherapies for lung and breast cancer, we reexamined breast lump biopsy and found they were all lung adenocarcinoma metastasis to the breast with the presence of an ALK rearrangement in one case and of ROS1 rearrangement in the other. Eventually these 2 patients were treated with crizotinib. Both the primary tumor and the metastasis of these 2 patients were significantly regressed.Conclusion:Whenever a diagnosis of a suspected tumor with sites at more than one organ is made, pathologic as well molecular pathologic examinations designated for organ-specific cancers should be done.
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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