DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Epithelioid Cell Uveal Melanoma — screening already-approved drugs against its 21-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEpithelioid Cell Uveal Melanoma maps to a 21-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 epithelioid cell uveal 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
tyrosyl-DNA phosphodiesterase 1 (TDP1) — TDP1 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 k8jdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6N0D · 1.453 Å · ligand 4-fluorobenzene-1,2-dicarboxylic acid (K8J). Experimental structure, not a prediction.
What the evidence adds up to
In a 2004 case report of a rapidly growing uveal melanoma in a 71-year-old woman, the tumour was composed of spindle B-cells and showed a 31.5-day doubling time. Immunohistochemistry detected p16 and Bcl-2 but not p53, and pRb was absent in tumour cells while present in normal retinal and choroidal cells. The authors concluded that the cell cycle protein profile suggested a more aggressive phenotype despite low histopathologic grade.
A 2018 study of 70 uveal melanoma patients quantified a small epithelioid cell component that ranged from 0% to 30% of tumour volume (median 1%). Thirty-nine tumours (55.7%) contained these cells. On univariate analysis, a small epithelioid cell component greater than 5% was associated with worse metastasis-free survival, along with mixed versus spindle cell type, higher lymphocytic and macrophage infiltration, and ciliary body involvement. On multivariate analysis, a small cell component greater than 5% was the strongest independent adverse prognostic factor. The small epithelioid cells were negative for HMB45, stem cell markers and CD3, and only focally and weakly positive for Melan A and SOX10.
A 2002 laboratory study tested transducible peptides targeting HDM2 and Bcl-2 in cultured uveal melanoma and retinoblastoma cells. The anti-Bcl-2 peptide induced apoptosis in tumour cells but also killed normal cells and caused retinal damage after intravitreal injection in a rabbit model. The anti-HDM2 peptide induced p53 accumulation, activated apoptotic genes, preferentially killed tumour cells, and caused minimal retinal damage; it also induced regression of human retinoblastoma cells in rabbit eyes. No clinical data in uveal melanoma patients were reported.
A 2005 prospective study with historical controls examined preenucleation radiotherapy (PER) in 167 uveal melanoma patients given 8 Gy in two fractions before enucleation, compared with 108 patients treated by enucleation alone. After a mean follow-up of 9.25 years, melanoma-related death occurred in 32.3% of the PER group and 40.7% of the enucleation-only group. Estimated 15-year melanoma-specific survival was 63.7% with PER versus 51.0% without; overall survival was 47.5% versus 25.2%. A survival difference favouring PER became evident after 48 months. Women had better outcomes in both groups. No abstract specifically addressed epithelioid cell uveal melanoma as a distinct subgroup in these trials.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Ophthalmology · 2002 · 97 citations
Transducible Peptide Therapy for Uveal Melanoma and Retinoblastoma
AbstractOBJECTIVE: To determine whether transducible peptides that inhibit the oncoproteins HDM2 and Bcl-2 may selectively kill uveal melanoma and retinoblastoma cells. METHODS: Peptides were tested by viability assay, flow cytometry, TUNEL (terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labeling) assay, Western blot analysis, and reverse transcription-polymerase chain reaction in cultured eye tumor cells and normal cells. Preclinical studies were performed in a rabbit xenograft model of retinoblastoma. MAIN OUTCOME MEASURES: Cell survival, apoptosis, gene expression, and tumor regression. RESULTS: The anti-Bcl-2 peptide induced apoptosis in tumor cells, but it also caused apoptosis in normal cells in culture and induced retinal damage after intravitreal injection. In contrast, the anti-HDM2 peptide induced rapid accumulation of p53, activation of apoptotic genes, preferential killing of tumor cells, and minimal retinal damage after intravitreal injection. The anti-HDM2 peptide also induced regression of human retinoblastoma cells in rabbit eyes. CONCLUSIONS: Peptide transduction is a promising new approach to molecular eye cancer therapy. Inhibition of HDM2 can selectively activate p53 in transformed cells and may be an effective strategy for inducing apoptosis in eye cancer cells with minimal damage to normal ocular tissues. CLINICAL RELEVANCE: Molecular characteristics of uveal melanoma and retinoblastoma may be used to design novel therapeutic agents that have greater specificity and fewer adverse effects than current therapies.
Archives of Ophthalmology · 2005 · 10 citations · open access
Reduced Melanoma-Related Mortality in Uveal Melanoma by Preenucleation Radiotherapy
AbstractBACKGROUND: Radiotherapy of an eye before enucleation, so called preenucleation radiotherapy (PER), of patients with uveal melanoma was initiated to reduce enucleation-induced systemic metastasis. Earlier studies with a short follow-up period have not demonstrated a significant effect on survival. OBJECTIVE: To study the effect of PER on melanoma-related mortality after more than 9 years of follow-up. DESIGN: In a prospective study, 167 patients with uveal melanoma were treated between 1978 and 1992 by irradiation with 800 rad (8 Gy) given in 2 fractions 2 days before enucleation. A group of 108 patients with uveal melanoma treated between 1971 and 1992 by enucleation only in the same hospital served as a historical control group. Patients were followed up until December 2002 or death. RESULTS: Melanoma-related death occurred in 32.3% of the PER-treated group and in 40.7% of the enucleation only group. Mean follow-up was 9.25 years. After 48 months of follow-up, a significant difference in survival became evident in favor of the PER group. The estimated 15-year survival rates for patients with melanoma in the PER group and enucleation only group were 63.7% and 51.0%, respectively. For patients dying of all causes, these percentages were 47.5% and 25.2%, respectively. In both groups, women had a better prognostic outcome than men. CONCLUSION: This study suggests that PER improves long-term survival in patients with uveal melanoma.
EXPRESSION OF CELL CYCLE RELATED PROTEINS IN A RAPIDLY GROWING UVEAL MALIGNANT MELANOMA
AbstractPURPOSE: To report the clinical and immunohistochemical findings of a rapidly growing uveal melanoma. METHODS: A 71-year-old Japanese woman was diagnosed with a juxtapapillary uveal melanoma by clinical examination. The tumor grew rapidly with a 31.5-day doubling time. An enucleation was performed, and immunohistochemical examination for cell cycle proteins was performed in addition to routine histopathologic examination. RESULTS: The melanoma cells were classified as spindle B-cells. The tumor cells were positive for HMB-45 protein, but negative for S-100 protein. The tumor showed immunohistochemical staining for p16 and Bcl-2, although p53 was not detected. Immunoreactivity for pRb was found in normal retinal and choroidal cells but not in the tumor cells. CONCLUSION: This report describes a unique case of rapidly growing uveal melanoma, which showed low histopathologic grade while the cell cycle protein immunohistochemical profile suggests a more aggressive phenotype. The evaluation of cell cycle proteins may be useful adjunctive method to enhance the understanding of uveal melanoma growth patterns.
Annals of Eye Science · 2018 · 0 citations · open access
AB045. Prognostic significance and characterization of small epithelioid cell population in uveal melanoma
AbstractBackground: Uveal melanoma (UM) is a malignant neoplasia that is composed of two main types of cells: spindle and epithelioid. There is a subset of neoplastic small epithelioid cells located predominantly in the infiltrative tumor margins or surrounding blood vessels. The aim of this study is to characterize and evaluate the correlation between the presence of these small epithelioid cells and clinical outcome. Methods: The clinical-pathological features of 70 UM patients were evaluated. The presence of small epithelioid cells was quantified based on percentage of tumor volume, and they were characterized using melanocytic markers (HMB-45, Melan A and SOX-10), stem cell markers (CD133, CD24 and CD38), and T cell lymphocytes (CD3). Univariate and multivariate analyses were conducted. Clinical follow up was available for all patients. Results: The ratio of small epithelioid cell components of all 70 tumors ranged from 0% to 30% (median, 1%). Thirty-nine tumors (55.7%) had areas with small epithelioid cells. Univariate analysis showed that mixed versus spindle cell, higher lymphocytic infiltration, macrophage infiltration, ciliary body involvement, and >5% of small epithelioid cell component had a significant negative impact on metastasis-free survival. Small epithelioid cell component >5% was present in 24 cases (34.3%). Of these, three were classified as spindle and 21 were mixed. Multivariate analysis revealed that a >5% small cell component was the most significant morphological adverse prognostic factor. Moreover, the small epithelioid cells were negative for HMB45, stem cell markers and CD3, and focally and weakly positive for MELAN A and SOX10. Conclusions: A high small epithelioid cell component is a strong negative prognostic indicator in patients with UM.
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.
