DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Uveal Melanoma — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleUveal Melanoma maps to a 45-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
approvedDasatinibApproved drug
Structures already discussed alongside uveal melanoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of EphA4 kinase domain — Dasatinib has a real, experimentally solved structure in complex with this target (PDB 2Y6O, 1.543 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet 1n1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Y6O · 1.543 Å · ligand Dasatinib (1N1). Experimental structure, not a prediction.
What the evidence adds up to
Uveal melanoma accounts for 5% of all melanoma diagnoses in the United States, with an age-adjusted risk of 5 per 1 million population. It is biologically distinct from cutaneous melanoma, with different risk factors, patterns of spread, molecular changes, and responses to systemic therapy. Once metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of uveal melanoma patients from those trials. Nearly half of primary uveal melanoma tumours metastasise, and there are currently no effective therapies for metastatic disease.
The Collaborative Ocular Melanoma Study (COMS) established that plaque brachytherapy and enucleation produce equivalent overall survival for medium-sized choroidal melanomas. A 2025 reanalysis of the COMS 12-year mortality data found 105 melanoma-related deaths in the brachytherapy arm and 98 in the enucleation arm (risk ratio 1.08, 95% CI 0.82–1.42). Achieving statistical significance would have required 31 additional deaths in the brachytherapy arm or 23 fewer in the enucleation arm; conversely, favouring brachytherapy would have needed 34 additional deaths in the enucleation arm or 27 fewer in the brachytherapy arm. The authors concluded the trial did not reveal a clinically meaningful survival difference and underscored the substantial mortality shifts required for statistical significance.
A 2020 integrative analysis of 10,678 SEER cases and 788 molecularly prognosticated patients modelled excess absolute risk of death as two waves. The first wave peaks at approximately 3 years and is negligible by 15 years, attributable to BAP1 mutant cases (204 of 355, 57.5%; 95% CI 52%–63%). The second wave peaks after 15 years, attributable to BAP1 wild-type SF3B1 mutant cases (60 of 355, 17%; 95% CI 13%–21%). A third group (91 of 355, 25.5%; 95% CI 21%–30%) showed a low flat excess risk time course. The overall statistical cured fraction of 60% is reached by approximately 25 years. The authors suggested that the benefits of ocular therapy for curing uveal melanoma may be questionable because statistical cures reflect deaths of poor prognosis cases and survival of good prognosis cases, and that changes in patient management may be needed to improve survival.
Despite decades of research, no systemic therapy has shown reliable efficacy in metastatic uveal melanoma. The discovery of mutations underlying uveal melanoma metastasis, growth, and survival has not yet translated into effective treatments. What remains missing are adequately powered randomised trials designed specifically for uveal melanoma rather than extrapolated from cutaneous melanoma, reliable biomarkers to stratify patients by risk before metastasis, and funding to move beyond the molecular understanding that has been in place since at least 2003.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 2016 · 446 citations · open access
Uveal melanoma: From diagnosis to treatment and the science in between
The Cancer Journal · 2012 · 109 citations · open access
Metastatic Uveal Melanoma
AbstractUveal melanoma is the most common primary intraocular cancer in adults. Nearly half of primary uveal melanoma tumors metastasize, but there are currently no effective therapies for metastatic uveal melanoma. The recent discovery of mutations that underlie uveal melanoma metastasis, growth, and survival provide a key to the molecular understanding of this disease. Much work is now underway to leverage this knowledge to develop effective therapies. This review summarizes recently discovered molecular features of uveal melanoma and therapies being explored to capitalize on this knowledge.
JAMA Ophthalmology · 2020 · 24 citations · open access
Estimating Cured Fractions of Uveal Melanoma
AbstractImportance: The extent to which uveal melanoma is cured by ocular therapy is not known. Objective: To estimate cured fractions (CF) of uveal melanoma using combination of institutional and Surveillance, Epidemiology, and End Results (SEER) data. Design, Setting, and Participants: Integrative analysis of 42 years of SEER data (1975-2016) with 25 years (1993-2018) of complementary institutional data. The analysis included SEER US patients and molecularly prognosticated patients in the United States and Europe. Three SEER databases (SEER-9, SEER-13, and SEER-18) were merged. A total of 10 678 SEER cases of uveal melanoma diagnosed from 1975 to 2016 using International Classification of Disease for Oncology morphology codes 8720-8790 (for melanoma) and site codes C69.2-4 (for choroid, ciliary body, and iris) were downloaded April 16, 2019. The institutional data included 5 institutional cohorts of 788 molecularly prognosticated patients (diagnosed prior to July 2019) with 3115 person-years at risk of death and 262 observed deaths. Main Outcomes and Measures: Excess absolute risks of death (EAR) and cured fraction (CF) indicates lifetime area under the EAR curve. These are applied to populations and subpopulations. Results: The SEER EAR, with sexes and races pooled, can be modeled as a sum of 2 waves. The first wave peaks at approximately 3 years and is negligible by 15 years, at which time the second wave peaks. Institutional data suggest that the first wave is owing to BAP1 mutant cases (204 of 355 [57.5%]; 95% CI, 52%-63%) and that the second wave is owing to BAP1 wild-type SF3B1 mutant cases (60 of 355 [17%]; 95% CI, 13%-21%). There is also a third group with a low flat EAR time course (91 of 355 [25.5%]; 95% CI, 21%-30%). The overall statistical CF of 60% is reached by approximately 25 years. Conclusions and Relevance: These findings suggest that the benefits of ocular therapy for curing uveal melanoma may be questionable because statistical cures reflect deaths of poor prognosis cases and survival of good prognosis cases. Changes in uveal melanoma patient management may be needed to improve survival.
AbstractIn the past decade, there have been impressive advances in our understanding of chromosomal, genetic and molecular alterations that occur in uveal melanoma. Nevertheless, a coherent picture of the molecular pathogenesis of this eye cancer is yet to emerge. Herein, we review the findings to date, discuss the insights they provide, and suggest future directions for molecular research in uveal melanoma.
Journal of Contemporary Brachytherapy · 2022 · 7 citations · open access
Radiological and clinical findings in uveal melanoma treated by plaque interventional radiotherapy (brachytherapy): Visual atlas and literature review on response assessment
AbstractUveal melanoma (UM) is the most common intra-ocular tumor in Caucasian adults and may derive from melanocytes. Historically, the first therapeutic approach to treat UM has been surgical removal of the eye, with obvious consequences in terms of function, cosmesis, and psychological impact on patients. Collaborative Ocular Melanoma Study (COMS) introduced the first uniform approach to perform interventional radiotherapy (IRT - brachytherapy) procedure in a standardized way that allowed to demonstrate equivalence of IRT with enucleation in terms of overall survival. Since this milestone, several international guidelines have been issued with regard to several technical aspects of this procedure, which has become the mainstream therapy worldwide. However, nowadays, there is still a lack of consensus about the criteria to definitively assess UM response after IRT. We present a collection of paradigmatic cases treated in our institution, and then discuss in detail the latest available evidence on the topic.
Acta Oncologica · 2022 · 5 citations · open access
Outcomes of fractionated CyberKnife radiosurgery in patients with choroidal malignant melanoma
AbstractObjective The aim of this study was to evaluate local tumor control and complication development rates of fractionated CyberKnife radiosurgery (CRS) in patients with choroidal melanoma.Methods A total of 29 patients with choroidal melanoma were treated with fractionated CRS at Ankara Oncology Research and Training Hospital, Department of Radiotherapy between May 2009 and December 2013. Patients were treated with CRS if the initial height of the choroidal melanoma was ≥ 6 mm, or juxtapapillary and/or juxtamacular tumors with a height of >2.5 mm. Ophthalmic examinations were performed at baseline and at months 3, 6, 9 and 15 after radiotherapy. Assessment of visual acuity and measurement of tumor base dimension and height using A-scan and B-scan echography were done at each visit.Results The mean age was 56 (27–75) years. Tumor was located on choroid in 23 and on ciliochoroid in 6 patients. 86.2% of all melanomas were classified as medium sized and 23.8% as large sized. A median total dose of 5000 cGy was applied. Median tumor height decreased from 7.5 mm at baseline to 4.4 mm at the last follow-up visit (p < 0.001). Median visual acuity decreased from 0.4 at baseline to hand motion (p < 0.001). One patient had been lost to the metastatic disease and one patient had been treated with enucleation due to recurrent tumor growth.Conclusion CRS is an effective and reliable local treatment modality in uveal melanoma.
ERK activation and monosomy 3 are associated with Src expression in uveal melanoma and may serve as biomarkers for Dasatinib treatment
AbstractAbstract Purpose Uveal melanoma (UM) leads to metastasis in up to 50% of the patients. Patients at risk are readily identified using an array of prognostic markers but an effective treatment is lacking. We recently identified Src as an important tyrosine kinase that conveys MAPK activation in UM. GNAQ/GNA11 mutations are the common denominators of oncogene signalling in UM and Src is a likely downstream kinase. We describe the preclinical analysis of Dasatinib, a known inhibitor or Src kinase, in UM. Methods Eight tumours were removed, cultured and exposed to Dasatinib treatment. proliferation and MAPK signalling were evaluated. Additionally, 36 UM samples were analyzed for Src/ERK signalling, GNAQ/GNA11 mutation status, chromosome 3 and known histological prognostic parameters. Results Growth arrest was observed in 5 of 8 UM cultures and molecular analysis indicated that Dasatinib inhibited MAPK via Src. Treatment efficacy associated with MAPK and Src kinase activity as UM cells with the highest Src activity and MAPK activation displayed the strongest growth inhibition. Furthermore, treatment responses tended to be better in UM cultures with monosomy 3. In the cohort of primary UM, Src expression was highly correlated with MAPK activation and monosomy 3. Conclusion We identified the Src family kinase inhibitor, Dasatinib, as a treatment option for UM. Dasatinib inhibits UM proliferation and may also inhibit UM progression as an association between Src and monosomy 3 was revealed. Consequently, monosomy 3 analysis in tumour tissue may suffice both the prognosis and choice of treatment.
Melanoma Management · 2025 · 1 citations · open access
Threshold analysis of mortality outcomes in the collaborative ocular melanoma study (COMS)
AbstractAIM: The collaborative ocular melanoma study (COMS) reported similar survival between plaque brachytherapy (a type of interventional radiotherapy) and enucleation for medium-sized choroidal melanomas. We aimed to quantify the mortality differences required to achieve statistical significance and assess the robustness of these thresholds. METHODS: We reanalyzed 12-year mortality data from COMS using threshold analysis to determine how many additional or fewer deaths in either treatment arm would shift the lower bound of the 95% confidence interval (CI) for the risk ratio above 1. RESULTS: At 12 years, there were 105 melanoma-related deaths in the brachytherapy arm and 98 in the enucleation arm (risk ratio 1.08, 95% CI 0.82-1.42). Achieving statistical significance would have required 31 additional deaths in the brachytherapy arm or 23 fewer in the enucleation arm; conversely, favoring brachytherapy would have necessitated 34 additional deaths in the enucleation arm or 27 fewer in the brachytherapy arm. These thresholds remained consistent across power levels and sensitivity scenarios. CONCLUSIONS: The COMS trial did not reveal a clinically meaningful survival difference. Our findings underscore the substantial mortality shifts required for statistical significance and highlight the challenges in detecting modest treatment effects in uveal melanoma trials.
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.
