DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for papillary adenocarcinoma — 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 modulePapillary adenocarcinoma 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 papillary adenocarcinoma 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
bone morphogenetic protein 2 (BMP2) — BMP2 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 ndgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2GOO · 2.2 Å · ligand 2-acetamido-2-deoxy-alpha-D-glucopyranose (NDG). Experimental structure, not a prediction.
What the evidence adds up to
A 2023 study of eight digital papillary adenocarcinomas identified two distinct pathogenic pathways. Four cases were painless, slow-growing dermal nodules with glandular structures, rare mitoses, and no necrosis; all four were positive for BRAF V600E by immunohistochemistry and negative for p16 and HPV in situ hybridisation. The other four cases were painful, rapidly growing deep dermal masses with solid papillary architecture, cellular necrosis, numerous mitoses, and squamoid differentiation; all were negative for BRAF V600E but showed strong p16 reactivity and positivity for low-risk HPV, with no high-risk HPV detected. The authors concluded that digital papillary adenocarcinomas with low-risk HPV infection exhibit aggressive clinical and high-grade morphological features, while those with BRAF V600E mutation have less aggressive behaviour.
A 2008 study using transgenic mouse mammary tumours compared gene-expression profiles of poorly differentiated carcinomas and highly differentiated papillary adenocarcinomas. The carcinoma tumours showed stronger expression of genes for integrins, cytoskeletal proteins, and calcium-binding proteins, along with higher expression in O-glycan synthesis, TGF-beta, activin, Notch ligands, and gamma-secretase components. The papillary adenocarcinomas showed higher expression of genes involved in cell-cycle arrest at G1 and response to DNA damage, with membranal accumulation of beta-catenin rather than nuclear translocation. The authors concluded that at least six metabolic pathways differ between the two phenotypes, with the carcinoma favouring cell adhesion, motility, and proliferation, and the papillary adenocarcinoma favouring cell-cell contact, polarity, and earlier cell-cycle arrest.
A 2020 commentary questioned whether a reported case of "papillary digital adenocarcinoma" with BRAF V600E mutation was correctly diagnosed, arguing the lesion was morphologically identical to cutaneous papillary adenocarcinoma in situ, a lesion previously called papillary eccrine adenoma. The commentary noted that staining for myoepithelial markers would show an intact myoepithelial cell layer around every duct or gland, and questioned whether "aggressive digital papillary adenocarcinoma" represents a distinct entity at all. A 2015 review of two case reports reiterated that aggressive digital papillary adenocarcinomas are rare malignant sweat gland tumours on the digits, often missed or delayed in diagnosis due to lack of pain and slow growth.
What remains missing is prospective data linking the molecular subtypes (BRAF mutation versus low-risk HPV) to actual recurrence or metastasis rates in patients, and any clinical trial testing whether these distinctions guide treatment. The mouse data on metabolic pathways has not been translated to human tumour stratification. No large series with long-term follow-up exists, and the diagnostic boundary between benign papillary eccrine adenoma and malignant digital papillary adenocarcinoma remains disputed, making patient selection for any future study uncertain.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Cutaneous Pathology · 2023 · 23 citations
Two distinct pathogenic pathways of digital papillary adenocarcinoma — <i>BRAF</i> mutation or low‐risk <scp>HPV</scp> infection
AbstractDigital papillary adenocarcinoma (DPA) is a rare neoplasm that can exhibit local recurrence and distant metastasis. We present a series of eight cases of DPA showing two distinct clinical presentations, morphologies, immunophenotypes, and molecular features. Four cases were characterized by painless, slow-growing nodules located on the digits. The lesions were small, well-defined, and confined in the dermis. Histopathologically, these tumors were composed of glandular structures lined by cuboidal epithelium with luminal papillary infoldings. Only rare mitotic figures and minimal squamoid differentiation were present, and cellular necrosis was absent. All four cases were positive for the BRAF V600E immunohistochemistry but negative for p16, low-risk and high-risk HPV in situ hybridization (ISH). In contrast, the remaining four cases were characterized by painful, rapidly growing masses on the digits. These four lesions were located in the deep dermis and consisted of a solid, tightly packed papillary architecture lined by atypical epithelioid cells with inconspicuous nucleoli. Cellular necrosis, numerous mitotic figures, and prominent squamoid differentiation were seen. All cases were negative for the BRAF V600E IHC. However, they showed strong, patchy to diffuse reactivity for p16 and were positive for low-risk HPV ISH and negative for high-risk HPV ISH. Our findings suggest that the current classification of DPA encompasses tumors that show two discrete pathogenic pathways - BRAF mutation or low-risk HPV infection. DPAs with low-risk HPV infection exhibit aggressive clinical features, high-grade morphology, marked squamoid differentiation, and wild-type BRAF. DPAs with BRAF V600E have less aggressive clinical features, low-grade morphologic findings, mild to absent squamoid differentiation, and negative HPV infection.
Clinical Cosmetic and Investigational Dermatology · 2015 · 12 citations · open access
Aggressive digital papillary adenocarcinoma &ndash; a rare malignant tumor of the sweat glands: two case reports and a review of the literature
AbstractAbstract: Aggressive digital papillary adenocarcinomas are rare malignant tumors often located on the digits of the hand. Due to lack of pain, slow growth, and an inconspicuous appearance, diagnosis is often missed or delayed. We report two cases and review the present literature to give recommendations for diagnosis and treatment. Keywords: aggressive digital papillary adenocarcinoma, tumor, sweat glands
Different gene-expression profiles for the poorly differentiated carcinoma and the highly differentiated papillary adenocarcinoma in mammary glands support distinct metabolic pathways
AbstractBACKGROUND: Deregulation of Stat5 in the mammary gland of transgenic mice causes tumorigenesis. Poorly differentiated carcinoma and highly differentiated papillary adenocarcinoma tumors evolve. To distinguish the genes and elucidate the cellular processes and metabolic pathways utilized to preserve these phenotypes, gene-expression profiles were analyzed. METHODS: Mammary tumors were excised from transgenic mice carrying a constitutively active variant of Stat5, or a Stat5 variant lacking s transactivation domain. These tumors displayed either the carcinoma or the papillary adenocarcinoma phenotypes. cRNAs, prepared from each tumor were hybridized to an Affymetrix GeneChip(R) Mouse Genome 430A 2.0 array. Gene-ontology analysis, hierarchical clustering and biological-pathway analysis were performed to distinct the two types of tumors. Histopathology and immunofluorescence staining complemented the comparison between the tumor phenotypes. RESULTS: The nucleus-cytoskeleton-plasma membrane axis is a major target for differential gene expression between phenotypes. In the carcinoma, stronger expression of genes coding for specific integrins, cytoskeletal proteins and calcium-binding proteins highlight cell-adhesion and motility features of the tumor cells. This is supported by the higher expression of genes involved in O-glycan synthesis, TGF-beta, activin, their receptors and Smad3, as well as the Notch ligands and members of the gamma-secretase complex that enable Notch nuclear localization. The Wnt pathway was also a target for differential gene expression. Higher expression of genes encoding the degradation complex of the canonical pathway and limited TCF expression in the papillary adenocarcinoma result in membranal accumulation of beta-catenin, in contrast to its nuclear translocation in the carcinoma. Genes involved in cell-cycle arrest at G1 and response to DNA damage were more highly expressed in the papillary adenocarcinomas, as opposed to favored G2/M regulation in the carcinoma tumors. CONCLUSION: At least six metabolic pathways support the morphological and functional differences between carcinomas and papillary adenocarcinomas. Differential gene-expression profiles favor cell adhesion, motility and proliferation in the carcinoma. Cell-cell contact, polarity, earlier cell-cycle arrest and DNA damage control are better displayed in the papillary adenocarcinoma.
American Journal of Dermatopathology · 2020 · 2 citations
Commentary on a Recent Article Entitled “a Case Report of Papillary Digital Adenocarcinoma With BRAFV600E Mutation and Quantified Mutational Burden”
AbstractTo the Editor: In a recent article, entitled “a case report of papillary digital adenocarcinoma with BRAFV600E mutation and quantified mutational burden,”1 Trager et al reported a case of a 63-year-old woman with a nodule on her forearm presented for more than 10 years. The lesion was diagnosed by the authors as “papillary digital adenocarcinoma.” According to the authors, biopsy of the lesion showed a proliferation of cells in the dermis forming glandular structures, some with papillary projections, presence of moderate cytologic atypia and mitotic figures. The authors stated that “although our case could be consistent with a papillary eccrine adenoma, we believe that the histological findings including moderate atypia and mitotic figures are more suggestive of papillary digital adenocarcinoma.” Based on the photomicrographs the authors provided, the lesion is best interpreted as cutaneous papillary adenocarcinoma in situ in our opinion. Cutaneous papillary adenocarcinoma in situ was first proposed by Chen and Asgari2 in 2014. Of note, such lesions were initially called papillary eccrine adenoma by Rulon and Helwig3 in 1977.These lesions, in our view, are morphologically identical to the micropapillary type of ductal carcinoma in situ in the breast.4 If the authors stain the lesion for myoepithelial markers, they will find that every duct or gland is surrounded by intact myoepithelial cell layer. Furthermore, whether the so-called aggressive digital papillary adenocarcinoma really represents a specific entity has been addressed previously.5
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.
