DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for dysplastic nevus — screening already-approved drugs against its 15-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDysplastic nevus maps to a 15-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 dysplastic nevus 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
NRAS proto-oncogene, GTPase (NRAS) — NRAS 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZIO · 1.55 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
In a multicentre retrospective cohort study of 438 patients (467 lesions) with moderately dysplastic nevi that had been excisionally biopsied but had positive histologic margins, no case developed into cutaneous melanoma at the biopsy site over a mean follow-up of 6.9 years. However, 100 patients (22.8%) developed a melanoma at a separate body site. A history of prior melanoma was strongly associated with this risk (odds ratio 11.74), as was having two or more biopsied dysplastic nevi (odds ratio 2.55). Central dermatopathologic review of 40 random cases showed agreement in 35 (87.5%); three cases were upgraded in atypia, one of which was reinterpreted as melanoma in situ, though that patient remained free of recurrence or melanoma after five years.
A 2015 survey of Canadian dermatologists found that the majority retain the term dysplastic nevus and do not reexcise lesions with mild to moderate atypia even when margins are positive. The survey reflects prevailing opinion rather than trial data. Earlier commentary from 1990 and 1994 noted that little evidence existed for managing dysplastic nevi in children, and that histologic criteria for dysplasia remained vague, with poor reproducibility among dermatopathologists even when they convened specifically to assess concordance.
No drug treatment for dysplastic nevi appears in any of these abstracts. The evidence base consists entirely of observational data and expert opinion. What is still missing are prospective trials with standardised histologic criteria, long-term follow-up protocols that distinguish between index-site progression and new primary melanomas, and any investigation of chemoprevention or topical therapy. The 2018 study provides some reassurance about observation for positive-margin moderately dysplastic nevi, but the 22.8% rate of subsequent melanoma at other sites underscores the need for better risk stratification and surveillance strategies, not for drug intervention.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
JAMA Dermatology · 2018 · 49 citations · open access
Risk of Subsequent Cutaneous Melanoma in Moderately Dysplastic Nevi Excisionally Biopsied but With Positive Histologic Margins
AbstractImportance: Little evidence exists to guide the management of moderately dysplastic nevi excisionally biopsied without residual clinical pigmentation but with positive histologic margins (hereafter referred to as moderately dysplastic nevi with positive histologic margins). Objective: To determine outcomes and risk for the development of subsequent cutaneous melanoma (CM) from moderately dysplastic nevi with positive histologic margins observed for 3 years or more. Design, Setting, and Participants: A multicenter (9 US academic dermatology sites) retrospective cohort study was conducted of patients 18 years or older with moderately dysplastic nevi with positive histologic margins and 3 years or more of follow-up data collected consecutively from January 1, 1990, to August 31, 2014. Records were reviewed for patient demographics, biopsy type, pathologic findings, and development of subsequent CM at the biopsy site or elsewhere on the body. The χ2 test, the Fisher exact test, and analysis of variance were used to assess univariate association for risk of subsequent CMs, in addition to multivariable logistic regression models. To confirm histologic grading, each site submitted 5 random representative slide cases for central dermatopathologic review. Statistical analysis was performed from October 1, 2017, to June 22, 2018. Main Outcomes and Measures: Development of CM at a biopsy site or elsewhere on the body where there were moderately dysplastic nevi with positive histologic margins. Results: A total of 467 moderately dysplastic nevi with positive histologic margins from 438 patients (193 women and 245 men; mean [SD] age, 46.7 [16.1] years) were evaluated. No cases developed into CM at biopsy sites, with a mean (SD) follow-up time of 6.9 (3.4) years. However, 100 patients (22.8%) developed a CM at a separate site. Results of multivariate analyses revealed that history of CM was significantly associated with the risk of development of subsequent CM at a separate site (odds ratio, 11.74; 95% CI, 5.71-24.15; P < .001), as were prior biopsied dysplastic nevi (odds ratio, 2.55; 95% CI, 1.23-5.28; P = .01). The results of a central dermatopathologic review revealed agreement in 35 of 40 cases (87.5%). Three of 40 cases (7.5%) were upgraded in degree of atypia; of these, 1 was interpreted as melanoma in situ. That patient remains without recurrence or evidence of CM after 5 years of follow-up. Conclusions and Relevance: This study suggests that close observation with routine skin surveillance is a reasonable management approach for moderately dysplastic nevi with positive histologic margins. However, having 2 or more biopsied dysplastic nevi (with 1 that is a moderately dysplastic nevus) appears to be associated with increased risk for subsequent CM at a separate site.
A Relation between Childhood Sun Exposure and Dysplastic Nevus Syndrome among Patients with Nonfamilial Melanoma
AbstractWe studied 117 patients with nonfamilial melanoma to determine whether melanoma patients with dysplastic nevus syndrome might be distinguished, on the basis of solar exposure, from melanoma patients without dysplastic nevus syndrome. Study participants were interviewed and received a skin examination, which included a total count of nevi, a standardized assessment of clinically atypical nevi, and the excision of each patient's clinically most atypical nevus. Based on the histologic review of the clinically most atypical nevus, each patient was classified as to whether dysplastic nevus syndrome was present or absent. Childhood sunburn with blistering and childhood recreational sun exposure were found to be associated with dysplastic nevus syndrome. The results suggest that childhood sun exposure increases risk of melanoma by initiating the melanoma precursor syndrome.
The Journal of Dermatologic Surgery and Oncology · 1988 · 17 citations
Skin Types in Dysplastic Nevus Syndrome
AbstractIn order to determine if individuals with dysplastic nevi (DN) are relatively more sun-sensitive than controls who do not have DN, the sun-reactivity skin types (based on the Harvard classification) were determined in these two groups. Compared with controls, sun-sensitive types were significantly overrepresented in the DN group. This is consistent with the hypothesis that the fundamental defect in the dysplastic nevus syndrome is the genetically unstable melanocyte, which is susceptible to neoplastic transformation induced by sunlight.
Journal of Cutaneous Medicine and Surgery · 2015 · 8 citations
Dysplastic Nevus
AbstractBACKGROUND: The management of dysplastic nevi is controversial. No studies have collected data regarding management of the lesion amongst Canadian dermatologists. OBJECTIVE: To provide a comprehensive review of what the prevailing opinions are, regarding treatment and terminology of dysplastic nevi, amongst Canadian dermatologists. METHODS: An online survey of 25 questions was e-mailed to 613 members of the Canadian Dermatology Association, in French and English. RESULTS: A total of 179 responses were received. Varying numbers of participants completed each question. The majority of participants think that the term dysplastic nevus should not be abandoned, and they indicated that they never reexcise lesions with mild to moderate atypia even when the margins are positive. CONCLUSIONS: The majority of Canadian dermatologists retain the use of the term dysplastic nevus and do not reexcise lesions with mild to moderate atypia even when the margins are positive.
AbstractIssues surrounding the diagnosis and management of the dysplastic nevus have sparked considerable controversy in the dermatologic literature. Despite the great amount of attention to this subject, little has been written about the problem as it relates to the pediatric patient. For this reason, we formulated a set of questions that we thought needed to be addressed, and sought answers from several dermatologists. The replies largely reflect personal opinions, as few data are available on which to base a standard approach to these lesions.
AbstractThe concept and significance of dysplastic nevus continues to evolve amid controversy regarding diagnostic criteria and reproducibility. Histologic criteria remain vague and vary from study to study. In the present study, the authors attempted to quantify concordance rates in the histologic diagnosis of melanocytic lesions.
Six dermatopathologists with diverse views of dysplastic nevi convened to assess dysplasia in nevi. There was no attempt to unify diagnostic criteria prior to the study. Each …
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.
