DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for familial melanoma — 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 moduleFamilial melanoma 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 familial melanoma 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
X-ray repair cross complementing 3 (XRCC3) — XRCC3 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9SVY · 2.6 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
In a population-based study of 2,659 subjects with family-history information from the Utah Cancer Registry (1973–1999), multivariate logistic-regression analysis found no association between sex, Breslow depth, Clark level, or survival and familial status. Age at first diagnosis of invasive melanoma was slightly lower in the high-familial-risk group (57 vs 60 years; P = .03), and more melanomas were diagnosed at age 30 or younger in that group (12% vs 6%; P < .001). No significant difference in the number of individuals with two or more primary malignant melanomas was detected (P = .2). The authors concluded that melanomas occurring in the context of an inherited susceptibility do not have a significantly different biologic behaviour.
An earlier Australian study of 1,149 cutaneous melanoma cases and their 7,666 first-degree relatives found statistically significant heterogeneity in family risk. Of 1,116 unrelated families, 53 (4.7%) contained significantly more melanoma cases than expected given family size and the age, sex, and birth cohort distributions of members. Probands over-reported melanoma among relatives, with a false positive reporting rate of 44.5% (216 false reports out of 485). In a multiple logistic regression model, only tanning ability, skin colour, and number of nevi remained significantly associated with high-risk family status. There were no significant overall differences between high-risk and other families in sites and ages at diagnosis of melanoma, although melanomas on variably sun-exposed sites (trunk and legs) were diagnosed earlier in the high-risk families, independent of stage at diagnosis.
Germline mutations of the CDKN2A gene on chromosome 9p21 are known to predispose to melanoma in a subset of melanoma-prone families. Approximately 8 to 12% of melanoma appears to be inherited in an autosomal dominant form. The review from 1998 notes that most early stage melanomas can be treated successfully by simple surgical excision, but patients with advanced disease are rarely cured even with aggressive chemotherapy or immunotherapy. The authors suggest that identification and surveillance of unaffected individuals with a genetic predisposition may lead to detection of early melanomas and a reduction in mortality.
What remains missing is prospective evidence that surveillance of mutation carriers or high-risk family members actually reduces melanoma mortality in a controlled trial. The population-based data show no survival difference by familial status, so the benefit of early detection in this group is inferred rather than proven. No randomised trial has tested whether genetic testing itself changes outcomes, and the cost-effectiveness of screening programmes for familial melanoma families has not been established in a randomised design. Patient stratification by CDKN2A mutation status has not been linked to a specific treatment that improves survival in advanced disease.
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 Clinical Oncology · 2005 · 101 citations
Population-Based Analysis of Prognostic Factors and Survival in Familial Melanoma
AbstractPURPOSE: Familial melanoma patients are reported to present with thinner melanomas, to be younger at the time of diagnosis, and to have a greater likelihood of developing multiple primary tumors. We sought to determine whether melanomas that occur in a familial setting demonstrate different prognostic and survival statistics relative to sporadic melanoma. PATIENTS AND METHODS: This population-based study used the Utah Cancer Registry and Utah Population Database to objectively evaluate prognostic and survival statistics of the familial melanoma population. From 1973 to 1999, there were 7,785 cases of invasive melanoma identified through the Utah Cancer Registry. These were linked to the Utah Population Database, resulting in 2,659 subjects with family-history information from which a familiality score could be calculated. Cases scored in the top ninth percentile were assigned as high familial risk, and the remaining 91% were considered low familial risk. RESULTS: Multivariate logistic-regression analysis found no association between sex, Breslow depth, Clark level, or survival and the familial status. Age at first diagnosis of invasive melanoma was slightly lower in the high-familial-risk group (57 v 60 years; P = .03). High-familial-risk subjects had more melanomas diagnosed at age 30 or younger (12% v 6%; P < .001). A significant difference in the overall number of individuals with two or more primary malignant melanomas was not detected among the groups (P = .2). CONCLUSION: These data suggest that melanomas occurring in the context of an underlying inherited susceptibility do not have a significantly different biologic behavior.
American Journal of Epidemiology · 1994 · 56 citations
Heterogeneity of Melanoma Risk in Families of Melanoma Patients
AbstractWhile it is recognized that relatives of melanoma patients are at increased risk for this disease, the source and extent of variation in melanoma risk between families of melanoma cases is unknown. Heterogeneity of familial melanoma risk was assessed among the families (comprising 7,666 first-degree relatives) of 1,149 cutaneous melanoma cases diagnosed in Queensland, Australia, between 1982 and 1987. The measure of familial melanoma risk was based on the number of cases of melanoma in the family in excess of those predicted from the age-, sex-, and birth cohort-specific cumulative incidences of melanoma among all relatives in the sample. Probands over-reported melanoma occurrence among their relatives, with a false positive reporting rate of 44.5% (216 false reports out of 485). Only medically verified cases among relatives were included in the analysis. There was statistically significant heterogeneity in family risk, with 53 (4.7%) of the total 1,116 unrelated families containing significantly more melanoma cases than expected considering the size of the family, and the age, sex, and birth cohort distributions of family members. In univariate analyses, members of the high-risk families were significantly more likely to have poor ability to tan, a propensity to sunburn, fair skin color, red hair, and many melanocytic nevi. When all variables were included simultaneously in a multiple logistic regression model, only the associations with tanning ability, skin color, and number of nevi remained significant. There were no significant differences overall between high-risk and other families in the sites and ages at diagnosis of melanoma, although melanomas on variably sun-exposed sites (trunk and legs) were diagnosed earlier in the high-risk families, independent of the stage at diagnosis.
Acquired Melanocytic Nevi in Childhood and Familial Melanoma
AbstractIMPORTANCE: In the surveillance of familial melanoma, the identification of children at greater risk of developing melanoma later in life would serve as a helpful tool. OBJECTIVE: To determine whether acquired melanocytic nevi in childhood are an indicator of risk of melanoma in children from families with familial melanoma. DESIGN, SETTING, AND PARTICIPANTS: A 20-year follow-up study of a cohort of children from families with familial melanoma. Phenotypical data on melanocytic nevi were collected from a random sample of 133 members of families with familial melanoma 2 to 18 years of age with variable risks of being a mutation carrier. More than 20 years of follow-up data (gene-carrier status, diagnosis of melanoma, and excisions of nevi) were collected. In a subgroup of 40 people, childhood phenotypical data were compared with data on nevus numbers in adulthood. Survival analyses, correlation analyses, and t tests were calculated to examine associations. MAIN OUTCOMES AND MEASURES: Nevus count and distribution in childhood were correlated with the occurrence of melanoma and mutation carrier status. RESULTS: Significant risk factors for melanoma were found, specifically in the group with the highest risk of being a mutation carrier: total number of atypical nevi in childhood (hazard ratio [HR], 1.21; 95% CI, 1.02-1.44; P = .03), the nevus count of atypical nevi on the buttocks (HR, 14.00; 95% CI, 2.94-66.55; P = .001), and the number of excisions during follow-up (HR, 1.27; 95% CI, 1.23-1.31; P < .001). The analysis also found a correlation between the distribution of nevi in childhood and adulthood and the distribution of melanomas (correlation, 0.89; 95% CI, 0.67-0.96; and correlation, 0.99; 95% CI, 0.98-1.00; P < .001, respectively for both). CONCLUSIONS AND RELEVANCE: Numbers and distribution of melanocytic nevi in childhood are major indicators of the risk of melanoma in patients from families with familial melanoma.
Journal of Cutaneous Medicine and Surgery · 1998 · 13 citations
Role of the Cyclin-Dependent Kinase Inhibitor <i>CDKN2A</i> in Familial Melanoma
AbstractBACKGROUND: Approximately 8 to 12% of melanoma appears to be inherited in an autosomal dominant form. Although most early stage melanomas can be treated successfully by simple surgical excision, patients with advanced disease are rarely cured even with aggressive chemotherapy and/or immunotherapy. OBJECTIVE: There is now compelling evidence that germline mutations of the CDKN2A gene on chromosome 9p21 predispose to melanoma in a subset of melanoma-prone families. In this article the evidence for the role of CDKN2A in the genesis of familial melanoma is reviewed and the implications of genetic testing in families with this disease are discussed. CONCLUSION: The identification and subsequent surveillance of unaffected individuals who have a genetic predisposition to melanoma may lead to the detection of early (curable) melanomas and to a reduction in mortality.
AbstractIn this review we have aimed to focus on the clinical management of familial melanoma patients and their relatives. Along this line three major topics will be discussed: (1) management/screening of familial melanoma families: what is advised and what is the evidence thereof; (2) variability of families worldwide with regard to clinical phenotype, including cancer spectrum and likelihood of finding germline mutations and (3) background information for clinicians on the molecular biology of familial melanoma and recent developments in this field.
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.
