DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for breast fibrocystic disease — screening already-approved drugs against its 8-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBreast fibrocystic disease maps to a 8-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 fibrocystic disease 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
progesterone receptor (PGR) — PGR 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 14beta,17alphadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1SQN · 1.451 Å · ligand (14beta,17alpha)-17-ethynyl-17-hydroxyestr-4-en-3-one (NDR). Experimental structure, not a prediction.
What the evidence adds up to
A 2019 study of 17 breast cancer patients who had prior benign biopsies showing fibrocystic changes found no significant somatic mutations in the fibrocystic tissue. The time between biopsy and invasive cancer averaged 5.3 years. In 9 of the 17 cancers, somatic mutations were found (most often PIK3CA, n=4; TP53, n=2), but none of these were present in the earlier mastopathy tissue. In one case an ERBB3 mutation was present in both tissues at a very low frequency in the mastopathy (<0.1%). Two other shared mutations could have been fixation artifacts. The authors concluded it remains unclear why fibrocystic disease confers increased breast cancer risk.
A 2015 review states that treatment of most fibrocystic breast disease is conservative, using herbal medicine, hormones, anti-hormones, vitamins, and enzyme therapy. Nodal forms are treated surgically. The review mentions the drug Epigalin® as a possible prophylactic measure in high-risk women. A 2017 review describes pathogenetic treatment aimed at preventing breast cancer and mentions the drug Progestogel® for treatment and prophylaxis.
A 2019 study of capsular fibrosis around breast implants analysed 40 human capsule samples (20 mild Baker I, 20 severe Baker IV). In severe fibrosis 1,543 genes were upregulated and 1,016 downregulated compared to mild cases. Macrophage activation and extracellular matrix genes were highly expressed, while myofibroblast genes were not significantly increased. In mouse models, over 80% of macrophages in the capsule expressed collagen 1, and lineage tracking showed these collagen-producing cells were derived from haematopoietic cells. The authors concluded that macrophages, not fibroblasts, are the predominant source of collagen in implant fibrosis.
What is missing: no randomised trial has tested any drug specifically for fibrocystic disease against placebo with cancer incidence as an endpoint. The genetic basis of the risk remains unexplained. The macrophage findings apply to implant capsules, not to fibrocystic breast tissue. No study has stratified patients by mutation status or mammographic density before testing a preventive agent. Funding for such a trial would need to be long-term, given the years between benign disease and cancer.
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 American Journal of Surgical Pathology · 1990 · 26 citations
Fibroadenomatoid Hyperplasia of the Male Breast
AbstractA 69-year-old man with congestive heart failure who had been treated with digoxin for 27 years and spironolactone for 4 years developed bilateral gynecomastia. Excised tissue contained multiple nodules. Histologically, the nodules showed a structural pattern corresponding to fibroadenoma of the female breast. This lesion, called "fibroadenomatoid hyperplasia," is probably caused by treatment with spironolactone. The lesion has not previously been described in tissue from the male breast.
Frontiers in Medicine · 2019 · 25 citations · open access
Genetic Alterations in Benign Breast Biopsies of Subsequent Breast Cancer Patients
AbstractBackground: Fibrocystic changes are associated with an increased risk of breast cancer. Genetic alterations have been found in fibrocystic changes with or without epithelial changes, suggesting that critical oncogenic events are occurring at an early stage. Methods: We investigated a unique collective of 17 breast cancer patients who, prior to the diagnosis of invasive breast cancer, underwent open surgical biopsy showing fibrocystic changes of the breast. The time span between biopsy for fibrocystic changes and invasive carcinoma ranged from 1 to 11 years (average 5.3 years). 10 (58.8%) of the patients had an ipsilateral invasive carcinoma, and 7 (41.2%) of the patients developed an invasive carcinoma of the contralateral breast. Massive parallel sequencing targeting genes frequently mutated in breast cancer was performed on the fibrocystic breast tissue as well as the ensuing cancer tissue. Results: In 9 cases, somatic mutations were found in the tumor tissue, the most prevalent being PIK3CA mutations (n=4), followed by TP53 mutations (n=2). None of these mutations were present in the previously removed mastopathy tissue. In one of the cases, an ERBB3 E928G mutation was present in the mastopathy as well as in the tumor tissue, with the variant allele frequency in the mastopathy being <0.1%. In two patients, we found two mutations (MAP3K1 L380fs and PIK3CA I391M respectively) present in the mastopathy as well as in the subsequent breast cancer. These two mutations, however, could also be due to fixation artifacts. Conclusion: Since no significant somatic mutations in the fibrocystic breast tissue, and only doubtful shared mutations between benign and associated cancer tissue were detected, it remains unclear why women with fibrocystic breast disease have a statistically significant increased risk of breast cancer. Further analyses, maybe on the level of gene expression, could help to clarify the role of these benign alterations in the development of breast cancer and help to identify women at greater risk of developing subsequent invasive cancer
Reproductive Endocrinology · 2015 · 5 citations · open access
Treatment of fibrocystic breast disease – a way to prevent breast cancer
AbstractThe issues of classification, etiology, pathogenesis, clinical presentation, diagnosis and treatment of fibrocystic breast disease in the context of the prevention of breast cancer are present in this article.Treatment of most cases of fibrocystic breast disease is carried by conservative methods. The most frequently used pathogenetic grounded herbal medicine, hormone therapy, anti-hormones, vitamins, enzyme therapy. Nodal forms of fibrocystic breast disease are subject to surgical treatment.An individual program of screening is developed for women, depending on the degree of breast cancer risk. Studies in recent years allow us to consider the use of such drug as Epigalin® for a prophylactic measure in high-risk women
Diffusive breast diseases: a new vector of targeted therapy A.
AbstractThe article describes the review of literature risk factors for fibrocystic disease (FCD), the role and place of individual risk factors such as mammographic density and cyclic mastalgia. The evaluation of significant clinical symptoms as a risk factor for breast cancer (BC) was made. The modern possibilities of diagnostics of FCD are considered. The modern recommendations on medical tactics are given. The pathogenetic treatment of FCD aimed at preventing breast cancer is described; The use of a Progestogel® drug for the treatment of FCD and breast cancer prophylaxis.
Plastic & Reconstructive Surgery Global Open · 2019 · 0 citations · open access
Abstract 133: Implant Fibrosis is Caused by a Unique Subgroup of Collagen Producing Macrophages
AbstractPURPOSE: All implanted medical devices stimulate collagen deposition resulting in a surrounding fibrotic capsule. Implants are frequently used for reconstruction, such as breast implants following mastectomy. The most common complication following breast implants is capsular fibrosis (CF), with its severity clinically measured by the Baker I-IV classification. Despite the clinical prevalence, the mechanisms underlying CF are still poorly understood and therapeutic interventions are limited. For the first time, we analyze human capsule samples to identify the pathways activated in human capsular fibrosis, and use animal models to clarify the mechanisms underlying the fibrotic process resulting in CF. METHODS: We have established the largest tissue bank worldwide for breast capsular tissues, including histological and clinical data. Consisting of over 600 breast tissues, this registry provides the opportunity to analyze mechanisms underlying CF. Using RNA analysis with a 2,559-gene probeset, the gene expression from a total of 40 patients was analyzed. 20 patients expressing the mildest form of capsular fibrosis (Baker I) were compared to 20 human samples of the most severe form of this disease (Baker IV). All breast capsule samples were obtained after implant-based revision surgery. To recreate CF within an animal model, miniature silicone implants were placed subcutaneously in Bl6-mice. Cells from the capsule were then isolated and characterized by fluorescence-activated cell sorting (FACS), single cell quantitative polymerase chain reaction (qPCR) and single cell RNA sequencing to determine the genetic profiles of those most responsible for fibrotic development. Further, en-bloc capsule was additionally resected for SEM, TEM, 3D-confocal imaging and several stains. RESULTS: 1,543 genes were upregulated and 1,016 were downregulated in Baker IV vs Baker I. Interestingly, genes regulating macrophage activation, macrophage surface markers and extracellular matrix (ECM) production were among the most highly expressed in Baker IV specimens. Conversely, we did not observe significant increases in myofibroblast genes. To determine whether our findings in the human fibrotic tissues were similar to murine capsules we used vav-reporter-mice for lineage tracking. Here we observed the recruitment of mainly immune cells in fibrotic capsule development and identified the presence of a hematopoietic-derived cell with distinct characteristics of macrophages, confirming their existence within the chronology of CF. To confirm this, we placed silicone implants into Bl6-mice. Surprisingly, in the murine capsules we found the predominant cells across different time-points were myeloid cells and not fibroblasts or endothelial cells. We were able to confirm that these macrophages could produce ECM at the protein level by subjecting the cells to FACS analysis. We found over 80% of the macrophages expressing collagen 1. Our findings were confirmed by analysis of immunohistochemistry stains of the fibrotic sections showing that F4/80+ macrophages deposited collagen. CONCLUSION: For the first time we demonstrate that collagen depositingmacrophages are responsible for CF by analyzing both patient samples and murine models. Taken together, our findings suggest that macrophages seem to be one of the predominant sources of ECM deposition in fibrotic capsules and may have promising therapeutic implications for the treatment of CF.
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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