DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for mucosal melanoma — screening already-approved drugs against its 47-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMucosal melanoma maps to a 47-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 mucosal 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
Mucosal melanoma of the head and neck has a 5-year survival of 17% and a 10-year survival of 5%, based on a review of over 1000 patients. Approximately 19% of patients present with lymph node metastasis, another 16% develop lymph node metastases after treatment, and 10% present with distant metastasis. Over 50% of patients experience local treatment failure, and salvage treatment is effective in only 25% of those cases. Patients with nasal mucosal melanoma have a 31% 5-year survival rate, whereas sinus melanoma patients have a 0% 5-year survival rate. A retrospective review of 14 patients found a 5-year survival rate of 14%.
Whole-exome sequencing of 19 mucosal melanomas found that KIT and NF1 were frequently comutated in 32% of mucosal cases, compared with 4% in cutaneous melanoma. Recurrent SF3B1 R625H/S/C mutations were identified in 7 of 19 patients (37%). In a separate sequencing study of 44 patients with anorectal or gynecological melanoma, the median tumour mutation burden was 1.75 mutations per Mb. MUC16 was the most frequently mutated oncogene at 25%, KIT at 20%, NRAS at 20%, NF1 at 20%, and BRAF at 11%. KMT2D mutation was found in 18.18% of patients, a previously unidentified finding. Patients with TP53 mutations had a median survival time of 19 months versus 50 months for those without (log-rank P = 0.006).
Only a small number of mucosal melanoma patients who harbour mutations in BRAF or KIT benefit from targeted therapy. Standard adjuvant therapy for mucosal melanoma has not been established. Surgery appears to have the greatest efficacy in management, though radiation therapy may play an increasingly important role. The MAPK pathway, PI3K/AKT pathway, cell cycle regulation, telomere maintenance, and RNA maturation process are key pathways altered in mucosal melanoma, and targeted therapy strategies are under investigation.
What is still missing are effective targeted therapies for the majority of patients who do not harbour BRAF or KIT mutations, prospective trials to establish standard adjuvant therapy, and molecular markers that can be used for early diagnosis. The genetic evolution from benign lesions to metastatic mucosal melanoma remains poorly understood, and the endogenous or exogenous risk factors that influence mucosal melanocyte transformation are ambiguous.
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 · 1997 · 320 citations
Malignant mucosal melanoma of the head and neck
AbstractBACKGROUND: Fortunately, primary malignant mucosal melanoma of the head and neck is a rare entity. A paucity of data elucidating the predictive factors as well as the unpredictable and aggressive biologic behavior of mucosal melanoma compound the vexing clinical situation. This review summarizes what the literature reveals about the epidemiology, patient survival, patterns of local recurrence, and local and distant metastasis of the disease. Over 1000 patients with this disease have been reported. Survivals at 5 and 10 years is 17% and 5%, respectively. Approximately 19% of patients present with lymph node metastasis and another 16% develop lymph node metastases after treatment, whereas 10% present with distant metastasis. Local metastasis does not affect survival; this is in sharp contrast with skin melanoma. Over 50% of patients experience local treatment failure, and salvage treatment is effective in only 25% of these cases. Local failure is the harbinger of distant metastases. Patients with nasal mucosal melanoma have a 31% 5-year survival rate, whereas sinus melanoma patients fare poorly, with a 0% rate of 5-year survival. METHODS: The authors conducted a retrospective review of 14 patients with characteristics similar to those in the literature in terms of outcome. RESULTS: The 5-year survival rate for these patients was 14%. Whole-body positron emission tomography was performed on 3 patients to detect metastatic disease. The patterns of local recurrence, distant metastasis, and survival for these patients were compared with the same data for patients described in the literature. CONCLUSIONS: Surgery appears to have the greatest efficacy in the management of mucosal melanoma, although radiation therapy may play an increasingly important role in the future.
Melanoma Research · 2017 · 185 citations · open access
Whole-exome sequencing identifies recurrent SF3B1 R625 mutation and comutation of NF1 and KIT in mucosal melanoma
AbstractMucosal melanomas are a rare subtype of melanoma, arising in mucosal tissues, which have a very poor prognosis due to the lack of effective targeted therapies. This study aimed to better understand the molecular landscape of these cancers and find potential new therapeutic targets. Whole-exome sequencing was performed on mucosal melanomas from 19 patients and 135 sun-exposed cutaneous melanomas, with matched peripheral blood samples when available. Mutational profiles were compared between mucosal subgroups and sun-exposed cutaneous melanomas. Comparisons of molecular profiles identified 161 genes enriched in mucosal melanoma (P<0.05). KIT and NF1 were frequently comutated (32%) in the mucosal subgroup, with a significantly higher incidence than that in cutaneous melanoma (4%). Recurrent SF3B1 R625H/S/C mutations were identified and validated in 7 of 19 (37%) mucosal melanoma patients. Mutations in the spliceosome pathway were found to be enriched in mucosal melanomas when compared with cutaneous melanomas. Alternative splicing in four genes were observed in SF3B1-mutant samples compared with the wild-type samples. This study identified potential new therapeutic targets for mucosal melanoma, including comutation of NF1 and KIT, and recurrent R625 mutations in SF3B1. This is the first report of SF3B1 R625 mutations in vulvovaginal mucosal melanoma, with the largest whole-exome sequencing project of mucosal melanomas to date. The results here also indicated that the mutations in SF3B1 lead to alternative splicing in multiple genes. These findings expand our knowledge of this rare disease.
Melanoma Management · 2018 · 119 citations · open access
Combatting Mucosal Melanoma: Recent Advances and Future Perspectives
AbstractMucosal melanomas are a rare subtype of melanoma and are associated with a particularly poor prognosis. Due to the rarity of the diagnosis, and the pace with which the management of cutaneous melanoma has evolved over recent years, there is little good evidence to guide management and evidence-based clinical guidelines are still in development in the UK. In this review we provide an overview of the management of mucosal melanoma, highlighting the critical differences between cutaneous and mucosal melanomas, before examining recent advances in the systemic treatment of this disease and likely future directions.
Frontiers in Oncology · 2021 · 76 citations · open access
Mucosal Melanoma: Pathological Evolution, Pathway Dependency and Targeted Therapy
AbstractMucosal melanoma (MM) is a rare melanoma subtype that originates from melanocytes within sun-protected mucous membranes. Compared with cutaneous melanoma (CM), MM has worse prognosis and lacks effective treatment options. Moreover, the endogenous or exogenous risk factors that influence mucosal melanocyte transformation, as well as the identity of MM precursor lesions, are ambiguous. Consequently, there remains a lack of molecular markers that can be used for early diagnosis, and therefore better management, of MM. In this review, we first summarize the main functions of mucosal melanocytes. Then, using oral mucosal melanoma (OMM) as a model, we discuss the distinct pathologic stages from benign mucosal melanocytes to metastatic MM, mapping the possible evolutionary trajectories that correspond to MM initiation and progression. We highlight key areas of ambiguity during the genetic evolution of MM from its benign lesions, and the resolution of which could aid in the discovery of new biomarkers for MM detection and diagnosis. We outline the key pathways that are altered in MM, including the MAPK pathway, the PI3K/AKT pathway, cell cycle regulation, telomere maintenance, and the RNA maturation process, and discuss targeted therapy strategies for MM currently in use or under investigation.
AbstractMucosal melanoma is a rare subtype of melanoma and associated with extremely poor prognosis. However, standard adjuvant therapy for mucosal melanoma has not been established. Some approaches have been studied to reduce the risk of recurrence in patients. These include adjuvant chemotherapy, immunotherapy, targeted therapy, and radiotherapy (RT). In this review we aim to summarize and evaluate the therapies in development.
Основные подходы к проектированию модели социально-экономического развития региона
AbstractMucosal melanomas are rare, often aggressive tumors that can arise at any mucosal site but most frequently occur in the head and neck, vulvovaginal, and anorectal regions. They have distinct biological, clinical, and histopathologic features, which have important management implications. Recent whole-genome sequencing studies have led to a greater understanding of the molecular landscape of mucosal melanomas and uncovered oncogenic drivers that could potentially be susceptible to therapeutic manipulation. The authors provide a brief overview of epidemiologic, clinical, and histopathologic features of mucosal melanoma, with particular emphasis on recent advances in understanding, which have arisen from analyzing their molecular landscape.
Research Square · 2023 · 0 citations · open access
Whole-exome sequencing reveals mutational profiles of anorectal and gynecological melanoma
AbstractAbstract Mucosal melanoma is a rare and highly malignant type of melanoma. Among the sites that mucosal melanoma arises, anorectal and gynecological melanoma has more aggressive behavior and worse prognosis. There was no effective therapy for mucosal melanoma at present. Only a small number of mucosal melanoma patients which harbor mutations in BRAF or KIT benefit from targeted therapy. So it’s an urgent need to identify more actionable mutations in mucosal melanoma. To identify more potential therapeutic targets in mucosal melanoma, 48 samples were collected from 44 patients with anorectal or gynecological melanoma and subjected to whole-exome sequencing. The tumor mutation burden was low with a median of 1.75 mutations per Mb. In chromosomal level, 1q, 6p and 8q of mucosal melanoma were significantly amplified while 9p, 10p, 10q, 16p and 16q were significantly deleted. Muc16 was the most frequently mutated oncogene in our samples(25%). The mutation frequency of KIT(20%) was comparable to the "triple-wild" genes-NRAS(20%), NF1(20%) and BRAF(11%). KMT2D mutation was found in 18.18% patients, which is previously unidentified. MAPK signaling pathway and lysine degradation were the most frequently mutated pathways. Moreover, patients with TP53 mutations tend to have worse clinical outcome (median survival time 19 vs. 50 months, log-rank P = 0.006). M 2000 ore mutated genes involved in MAPK signaling pathway were identified, which expand the patients potentially benefit from ample MAPK inhibitors. KMT2D could be a potential therapeutic target. Moreover, TP53 could be a potential prognosis marker for mucosal melanoma.
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.
