DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Conjunctival Melanoma — 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 moduleConjunctival Melanoma 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 conjunctival 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
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
Conjunctival melanoma is a rare ocular malignancy with a lethal potential. In a Mexican cohort of 22 patients treated between 1985 and 2006, disease-free survival at five years was 51%, and overall survival at five and ten years was 50% and 37%, respectively. The average tumour size was 20.4 mm; 36% of patients underwent orbital exenteration, and 23% had wide excision alone. A 2004 review stated that surgical excision with adjuvant cryotherapy is usually effective for most lesions, and that extensive flat primary acquired melanosis with atypia may be managed with mitomycin C. The same review noted that systemic metastases may already have occurred in patients with advanced disease.
No therapy has been approved specifically for conjunctival melanoma. Analysis of 67 tumour samples classified conjunctival melanoma into BRAF-mutated (25%), RAS-mutated (19%), NF1-mutated (33%), and triple-wild-type tumours, a pattern similar to cutaneous melanoma. The authors of that study proposed that inhibitor therapy and immunotherapy, both successful in skin melanoma, could be considered valid options for conjunctival melanoma patients, but this remains a proposal, not a proven treatment.
Resistance to immunotherapy is a known problem. In melanoma cell lines and TCGA data, CDKN2A-associated JAK2 losses occurred in more than 60% of samples, and allelic JAK2 loss appears early in disease development. Inactivating mutations in single tumour clones can then establish JAK2 deficiency, which contributes to immunotherapy resistance. Non-genetic mechanisms, including an epithelial-to-mesenchymal transition-like phenotypic switch, have also been linked to acquired resistance to interferon-gamma and to unresponsiveness to both targeted inhibitors and immune-modulating antibodies.
What is still missing is a standardised treatment protocol for conjunctival melanoma, as noted in a 2025 narrative review. No randomised trial has tested either targeted therapy or immunotherapy specifically for this disease. Patient stratification by genetic subtype (BRAF, RAS, NF1, triple-wild-type) and prospective screening for JAK2 alterations have not been incorporated into any completed trial. Funding for a dedicated multicentre trial, and a design that accounts for the rarity of the disease, remain absent.
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 Control · 2004 · 77 citations
Malignant Melanoma of the Conjunctiva
AbstractBACKGROUND: Conjunctival melanoma is a relatively rare ocular malignancy with substantial associated morbidity and mortality. METHODS: More than 100 articles on conjunctival melanoma were reviewed, including most of the relevant recent publications cited in a current MEDLINE search. The author's experience with conjunctival melanomas is also incorporated in this review. RESULTS: Recognition of their precursor lesions at an early stage is important. Staging of the disease by sentinel lymph node biopsy is now advocated in some centers. Surgical excision with adjuvant cryotherapy and alcohol corneal epithelialectomy is usually effective in eradicating most of these lesions. Extensive cases of flat primary acquired melanosis with atypia may be managed with mitomycin C. Multifocal and advanced melanoma, especially in cases showing intraocular or orbital invasion, may require exenteration and/or radiotherapy to adequately extirpate the neoplasm locally. However, systemic metastases already may have occurred in these patients with advanced disease. CONCLUSIONS: Conjunctival melanoma is a condition of concern because of its rarity and lethal potential. Advances in the understanding and management of this neoplasm have markedly reduced the mortality and possibly the morbidity associated with this malignancy.
Arquivos Brasileiros de Oftalmologia · 2014 · 9 citations · open access
Conjunctival melanoma: survival analysis in twenty-two Mexican patients
AbstractPURPOSE: To describe the cases of conjunctival melanoma (CM) and report the disease-free interval (DFI) and overall survival (OS). METHODS: The charts of 22 patients who were admitted to two hospitals between 1985 and 2006 were reviewed for pertinent data, including demographics, site of involvement in the conjunctiva and sub-sites, surgical treatment, and adjuvant treatment. RESULTS: There were 10 (45.45%) males and 12 (54.55%) females. Mean age was 52.3 years. In this group, 15 patients (68.1%) involved the bulbar conjunctiva, and 7 (31.9%) involved the palpebral conjunctiva. Of the 22 patients, 72.72% had a history of conjunctival melanosis. The average tumor size was 20.4 mm. Eight (36.36%) patients underwent orbital exenteration, 2 (9.06%) had enucleation, 5 (22.72%) had wide excision of the lesion followed by radiotherapy, 2 (9.06%) had orbital exenteration with neck dissection, and the remaining 5 patients (22.72%) were considered adequately treated only with wide excision. Eight (36.36%) patients received adjuvant treatment. Disease-free survival at 5 years was 51% and the overall survival at 5 and 10 years was 50% and 37%, respectively. CONCLUSION: Conjunctival melanoma is a rare entity. Tumor behavior is aggressive, and the optimal treatment is surgery with adjuvant therapy.
Pigment Cell & Melanoma Research · 2025 · 8 citations · open access
Conjunctival Melanoma: A Narrative Review of Current Knowledge
AbstractThis review explores the current literature on conjunctival melanoma, a rare and complex periocular neoplasm, emphasizing the absence of a standardized treatment protocol and the associated management challenges. It examines the clinical, genetic, and histological features of conjunctival melanoma, alongside diagnostic methodologies and treatment strategies, drawing on the most recent bibliographic data. The literature was systematically reviewed using the PubMed database, offering insights into future research directions and highlighting innovative treatment approaches, particularly for advanced-stage disease.
DuEPublico (University of Duisburg-Essen) · 2021 · 0 citations · open access
Genomic and non-genomic alterations in melanoma contributing to disease progression and therapy resistance
AbstractMelanoma is an aggressive cancer that arises from transformed melanocytes of the skin and the ocular region, the uvea or conjunctiva. Two main therapies are currently applied to patients with cutaneous melanoma, small molecule inhibitors blocking dysregulated oncogenic pathways (in case of BRAFV600E mutant melanoma), and antibody-based immunotherapy, boosting cytotoxic T cell responses against cancer cells. So far, none of these therapies has been approved for conjunctival melanoma. Given the rarity of this disease, it has been difficult in the past to thoroughly study the molecular mechanisms and genetic alterations driving this type of melanoma. By analyzing a large cohort of 67 tumor samples, we aimed to elucidate recurrent genetic alterations in conjunctival melanoma. Targeted next-generation sequencing was performed covering genes recurrently mutated in cutaneous and uveal melanoma. This led to the identification of NF1 mutations in conjunctival melanoma, frequently detected in tumors lacking BRAF and RAS mutations. Based on these results, we proposed the classification of conjunctival melanoma into BRAF-mutated (25%), RAS-mutated (19%), NF1-mutated (33%) and triple-WT tumors, similar to cutaneous melanoma (paper Scholz et al., British J Cancer, 2018, in this thesis). Overall, our study provides insights into the mutational make-up of conjunctival melanoma and reveals the genetic similarities between cutaneous and conjunctival melanomas. Given the therapeutic success of inhibitor therapy and immunotherapy in skin melanoma, we propose both therapies can be considered as a valid option for patients suffering from conjunctival melanoma. As indicated above, T cell-based immunotherapy of cutaneous melanoma has achieved great success over the past few years. But approximately half of the treated patients are intrinsically resistant or acquire resistance to therapy, indicating the urgent need to elucidate resistance mechanisms. The T cell-derived cytokine IFNγ plays a fundamental role in tumor cell killing under immunotherapy. Inactivation of the kinase JAK2, an IFNγ signaling pathway component, is known to contribute to immunotherapy resistance in tumor cells. In Horn, Leonardelli et al., we provide insight into the evolution of JAK2 deficiency. The JAK2 locus maps closely to the CDKN2A locus, encoding the tumor suppressor p16 on chromosome 9p. Allelic CDKN2A loss is an important step in melanoma development and caused by large deletions on chromosome 9p. Analyzing SNP array data of 46 melanoma cell lines and copy number data of the TCGA melanoma cohort (n= 367), we found CDKN2A-associated JAK2 losses in the majority of samples analyzed (> 60%). Thus, allelic JAK2 loss occurs early in development of the disease, followed by inactivating gene mutations in single tumor clones finally establishing JAK2 deficiency (paper Horn, Leonardelli et al., JNCI, 2018, in this thesis). Our results suggest that screening of tumor lesions for genetic JAK2 alterations could be a valuable strategy to identify patients with an enhanced risk of developing immunotherapy resistance. While the contribution of genetic alterations to IFNγ resistance is now well accepted, the role of non-genetic mechanisms is poorly defined. We postulated that non- genomic mechanisms could protect melanoma cells from IFNγ-induced apoptosis thereby interfering with the efficacy of immunotherapy. To study this, we established IFNγ-resistant variants from IFNγ-sensitive parental tumor cells. The sensitive and resistant tumor cell pairs were analyzed for transcriptional signatures associated with resistance to cytokine-induced apoptosis and phenotypic alterations were confirmed at the protein level. This led to the identification of an EMT (epithelial to mesenchymal transition)-like phenotypic switch in cells with acquired resistance to IFNγ going along with the downregulation of IFNγ signaling pathway genes (paper Leonardelli et al., unpublished, in this thesis). Interestingly, the EMT signature has previously been reported to be associated with unresponsiveness to both treatment with targeted inhibitors and immune-modulating antibodies, suggesting a broader relevance of our findings for melanoma therapy. In summary, the different studies of this thesis provide further insight into the genetic and phenotypic heterogeneity of melanoma cells and its role in resistance to immunotherapy, which should guide therapeutic decisions to improve the clinical outcome of patients.
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.
