DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for epidermal appendage tumor — screening already-approved drugs against its 39-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEpidermal appendage tumor maps to a 39-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 epidermal appendage tumor 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
isocitrate dehydrogenase (NADP(+)) 2 (IDH2) — IDH2 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 ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5I96 · 1.55 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 retrospective study of 33 patients (10 male, 23 female) with skin appendageal tumours found that eccrine tumours were most common (17 cases, 51.5%), followed by hair-differentiation tumours (12 cases, 36.36%), sebaceous tumours (2 cases, 6.06%), and apocrine tumours (2 cases, 6.06%). Syringoma accounted for 14 of the eccrine cases (42.42% of all tumours), and trichoepithelioma for 9 of the hair tumours (27.27%). No malignant change was observed in any of the 33 tumours. The authors note that appendageal skin tumours are relatively uncommon and that histopathology is mandatory for diagnosis.
Earlier work on epidermal carcinogenesis distinguishes two stages: initiation, in which some epidermal cells become latent neoplastic cells, and promotion, which allows evolution into a neoplasm. A 1985 review argues that the epidermal hyperplasia produced by tumour promoters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) is a regenerative hyperplasia, preceded by epidermal damage. The review cites evidence that repeated wounding or abrasion can promote epidermal carcinogenesis in initiated mouse skin, and that hyperplasia-producing agents that do not promote tumours produce a different kind of hyperplasia. The same review suggests that hyperplasia may be the mechanism for tumour promotion in other organs, including liver, bladder, and intestine.
A 1983 review of epidermal biology notes that some epidermal tumours contain a low molecular weight keratin also found in fetal epidermis, and that certain cell-surface antigens such as pemphigus antigen may be absent in skin cancers. It reports that a population of basal "dark" cells increases after treatment with tumour-promoting phorbol esters, and that two-stage carcinogenesis can now be studied in tissue culture. A 2011 study examined EGF receptor and ras oncogene product p21ras in normal skin and in keratoacanthoma, solar keratosis, Bowen's disease, squamous cell carcinoma, basal cell carcinoma, and extramammary Paget's disease. EGF receptors were found in proliferating layers where DNA-replicating cells localise, while p21ras was found in more differentiated layers. The authors conclude that EGF receptor expression is closely associated with cellular proliferation, and p21ras may play a role in differentiation.
What is still missing is any clinical trial testing a drug specifically for epidermal appendage tumours, any patient stratification by tumour subtype or molecular marker, and any funding directed at repurposing existing compounds for this heterogeneous group of tumours. The available evidence is limited to descriptive histopathology and basic biology from the 1980s and 2000s, with no controlled treatment data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Critical Reviews in Toxicology · 1985 · 84 citations
Regeneration and the mechanism of epidermal tumor promotion
AbstractChemically induced epidermal carcinogenesis is often divided into two stages: initiation, which involves the conversion of some epidermal cells into latent neoplastic cells, and promotion, which allows the evolution of this neoplastic change into the formation of a neoplasm. The hallmark of epidermal tumor promotion is the transformation of the normal epidermis into a hyperplastic epidermis. A major unanswered question about epidermal tumor promotion is whether the epidermal hyperplasia that characterizes promoted skin is a regenerative epidermal hyperplasia resulting from damage produced by the promoter. The opinion currently held is that the epidermal hyperplasia produced by tumor promoters is not simply a regenerative epidermal hyperplasia and possesses characteristics which a regenerative hyperplasia does not have, enabling it to evolve into an epidermal neoplasm. The purpose of this review is to present recent evidence which strongly suggests that promoter-induced epidermal hyperplasia is a regenerative hyperplasia. Three principal lines of evidence are reviewed. The first demonstrates that an epidermal regenerative hyperplasia repeatedly produced by wounding or abrasion can promote epidermal carcinogenesis in the initiated skin of mice. The second line of evidence demonstrates that the epidermal hyperplasia produced by the application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), the most powerful and widely used promoter of skin carcinogenesis, is preceded by damage to the epidermis. This strongly suggests that the epidermal hyperplasia which ensues is a regenerative hyperplasia. Thirdly, evidence is presented which demonstrates that hyperplasia-producing agents which do not promote, produce an epidermal hyperplasia which is different from that produced by tumor promoters. Finally, the review discusses the evidence which suggests that the production of a hyperplasia may be the mechanism for tumor promotion in other organs, such as the liver, bladder, and intestine.
The International Journal of Developmental Biology · 2004 · 69 citations
The different steps of skin formation in vertebrates.
AbstractSkin morphogenesis occurs following a continuous series of cell-cell interactions which can be subdivided into three main stages: 1- the formation of a dense dermis and its overlying epidermis in the future appendage fields (macropattern); 2- the organization of these primary homogeneous fields into heterogeneous ones by the appearance of cutaneous appendage primordia (micropattern) and 3- cutaneous appendage organogenesis itself. In this review, we will first show, by synthesizing novel and previously published data from our laboratory, how heterogenetic and heterospecific dermal/epidermal recombinations have allowed us to distinguish between the respective roles of the dermis and the epidermis. We will then summarize what is known from the work of many different research groups about the molecular signaling which mediates these interactions in order to introduce the following articles of this Special Issue and to highlight what remains to done.
Indian Journal of Dermatology Venereology and Leprology · 2008 · 65 citations · open access
A clinicopathologic study of skin appendageal tumors
AbstractBACKGROUND: Appendageal skin tumors belong to a heterogenous group of tumors with specific histopathology. The aim of this study is to determine the pattern of appendageal tumors in skin biopsies done in our department. METHODS: This is a 3-year retrospective descriptive study of all patients who were diagnosed to have skin appendageal tumors in our department, and the diagnoses were confirmed by histopathology. The tumors were classified as eccrine, hair, sebaceous, and apocrine after a detailed examination of routine hematoxylin and eosin sections. RESULTS: The total number of cases in the study was 33-10 males and 23 females. Tumors with eccrine differentiation constituted the maximum, 17 cases (51.5%); followed by tumors with hair differentiation, 12 cases (36.36%); tumors with sebaceous differentiation, 2 cases (6.06%); and apocrine tumors, 2 cases (6.06%). Syringoma constituted the commonest eccrine tumor, 14 cases (42.42%); while trichoepithelioma was the commonest hair tumor, 9 cases (27.27%). The other eccrine tumors were eccrine spiradenoma, 2 cases (6.06%); and nodular hidradenoma, 1 (3.03%). The other hair tumors were pilar cyst, 2 (6.06%); and pilomatricoma, 1 (3.03%). The sebaceous tumors constituted 2 cases (6.06%) of nevus sebaceous. Syringocystadenoma papilliferum, 1 (3.03%); and cylindroma, 1 (3.03%), constituted the apocrine tumors. CONCLUSIONS: Appendageal skin tumors are relatively uncommon. Histopathology is mandatory for the diagnosis. No tumor showed malignant change in this study.
Metastatic cutaneous squamous cell carcinoma treated successfully with surgery, radiotherapy and S‐1/cisplatin chemotherapy
AbstractPrimary cutaneous squamous cell carcinoma (SCC) is a malignant tumor that arises from keratinizing cells of the epidermis or its appendages. We present a patient with cutaneous SCC on the left instep with metastases to multiple lymph nodes in the para-aortic, iliac and groin region. We chose a combination of surgery and concurrent chemoradiotherapy. The chemotherapeutic agent S-1/cisplatin was selected based on results of the histoculture drug response assay. The patient responded dramatically to this multidisciplinary treatment and complete remission was achieved.
Recent advances in epidermal biology: Relevance to epidermal malignancies
AbstractRecent advances in the biology of the epidermis increase our understanding of skin cancer. Epidermal tissue culture demonstrates that cells from epidermal malignancies retain their malignant characteristics. Some epidermal tumors contain a low molecular weight keratin as a major structural protein; a low molecular weight keratin is a characteristic of fetal epidermis as well. Certain epidermal cell-surface antigens, such as the pemphigus antigen, may be absent in skin cancers. A population of long-lived skin cells may be the site for genetic alterations that eventually produces skin cancers. A population of basal "dark" cells is increased after treatment with tumor promoting agents such as phorbol esters. Two-stage (initiation, promotion) epidermal carcinogenesis can now be studied in tissue culture. Several components of the complex multilayered basement membrane zone are produced by epidermal cells. Malignancies of epidermal cells may extend beyond the basement membrane zone by disordered synthesis of the zone or by producing enzymes including collagenases that alter the zone.
Minerva: Revista del Círculo de Bellas Artes · 2011 · 0 citations
Pasaje de jardines abiertos: entrevista con José María Sánchez-Verdú
AbstractThe localization of DNA replicating cells, epidermal growth factor (EGF) receptor-expressing cells and ras oncogene product p21 (p-21ras) positive cells were examined in various skin tumours to elucidate the role of EGF receptor and p21ras in the epidermis. Normal skin, keratoacanthoma (KA), solar keratosis (SK), Bowen's disease (BD), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and extramammary Paget's disease (PD) were studied. EGF receptors were seen in proliferating layers, where DNA replicating cells localize, but p21ras was found in the more differentiated layers. We conclude that EGF receptor expression is closely associated with cellular proliferation, but p21ras may play a role in the differentiation of cells in various skin tumours.
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.
