DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for nodular melanoma — screening already-approved drugs against its 49-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNodular melanoma maps to a 49-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 nodular 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
fibroblast growth factor receptor 4 (FGFR4) — FGFR4 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 1~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8KH8 · 1.49 Å · ligand 1-[4-[(1~{R})-1-[3,5-bis(chloranyl)pyridin-4-yl]ethoxy]-5-cyano-pyridin-2-yl]-3-[6-methanoyl-5-[(4-methyl-2-oxidanylidene-piperazin-1-yl)methyl]-3-(2-morpholin-4-ylethoxy)pyridin-2-yl]urea (VVW). Experimental structure, not a prediction.
What the evidence adds up to
Nodular melanoma is the second most common melanoma subtype and is defined by early vertical growth rather than the initial radial growth seen in other subtypes, giving it a more aggressive clinical phenotype. Surgical excision with wide margins remains the gold standard of therapy, but the prognosis in later stages is described as dismal compared with other subtypes. A better understanding of the molecular pathophysiology that drives this early aggressive behaviour is considered necessary for developing effective therapeutics for advanced disease.
A nationwide Dutch study using the Melanoma Treatment Registry compared 1086 patients with advanced nodular melanoma (stage IIIc and IV) against 2246 patients with advanced superficial spreading melanoma. Distant metastasis-free survival was significantly shorter for nodular melanoma patients at 1.9 years (95% CI 0.7–4.2) versus 3.1 years (95% CI 1.3–6.2) for superficial spreading melanoma (p < 0.01). However, multivariate survival analysis for first-line immunotherapy (anti-CTLA-4 and/or anti-PD-1) gave a hazard ratio of 1.0 (95% CI 0.85–1.17), and for BRAF/MEK inhibitors a hazard ratio of 0.95 (95% CI 0.81–1.11). The authors concluded that the efficacy of systemic therapy did not differ between the two subtypes, and that the worse overall survival in nodular melanoma is mainly driven by a greater propensity for metastatic outgrowth after primary diagnosis.
A smaller prospective study from 1998–2003 examined sentinel lymph node biopsy outcomes in 94 melanoma patients (mean Breslow thickness 28 mm; 38% nodular subtype). Among 19 relapses, 10 recurred in the same nodal basin. Of those 10 nodal recurrences, six occurred in patients who had a negative sentinel node, and five of those six (83%) were nodular melanoma histologically. The mean melanoma depth in these six patients was 246 mm (range 151–360 mm). The study indicated that local recurrence occurs more often in sentinel-node-negative patients with nodular melanoma and called for further evaluation of the inclusion criteria for sentinel mapping.
What remains missing is a molecular understanding of why nodular melanoma metastasises earlier and more aggressively, and whether that biology can be targeted separately from the pathways addressed by current immunotherapy and BRAF/MEK inhibitors. No trial has yet stratified nodular melanoma patients by molecular subtype or designed a therapy specifically for its vertical growth phase. Funding for such mechanistic work and for clinical trials that recruit nodular melanoma patients as a distinct cohort is lacking.
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 Dermatology and Skin Science · 2021 · 8 citations · open access
Nodular Melanoma: A Review of Pathogenesis, Presentation, Diagnosis, and Treatment
AbstractNodular melanoma is the second most common subtype of melanoma. Unlike other subtypes, nodular melanoma is characterized by early vertical growth rather than the typical initial radial growth of most melanomas. As a result, nodular melanoma presents clinically in a more aggressive phenotype. Given its more aggressive nature and intrinsic ability to mimic benign lesions, a modified acronym has been developed to allow clinicians to better evaluate, diagnose and treat nodular melanoma in earlier stages. Surgical excision with wide margins is the gold standard of nodular melanoma therapy; however, an emphasis in early detection, diagnosis, staging, and treatment needs to be emphasized among clinicians due to its dismal prognosis in later stages, as compared to other subtypes. A better understanding of the molecular pathophysiology that allows nodular melanoma to act aggressively very early in diagnosis is necessary for the development of therapeutics that may effectively target lesions in more advanced stages.
Systemic Therapy in Advanced Nodular Melanoma versus Superficial Spreading Melanoma: A Nation-Wide Study of the Dutch Melanoma Treatment Registry
AbstractNodular melanoma (NM) is associated with a higher locoregional and distant recurrence rate compared with superficial spreading melanoma (SSM); it is unknown whether the efficacy of systemic therapy is limited. Here, we compare the efficacy of immunotherapy and BRAF/MEK inhibitors (BRAF/MEKi) in advanced NM to SSM. Patients with advanced stage IIIc and stage IV NM and SSM treated with anti-CTLA-4 and/or anti-PD-1, or BRAF/MEKi in the first line, were included from the prospective Dutch Melanoma Treatment Registry. The primary objectives were distant metastasis-free survival (DMFS) and overall survival (OS). In total, 1086 NM and 2246 SSM patients were included. DMFS was significantly shorter for advanced NM patients at 1.9 years (CI 95% 0.7−4.2) compared with SSM patients at 3.1 years (CI 95% 1.3−6.2) (p < 0.01). Multivariate survival analysis for immunotherapy and BRAF/MEKi demonstrated a hazard ratio for immunotherapy of 1.0 (CI 95% 0.85−1.17) and BRAF/MEKi of 0.95 (CI 95% 0.81−1.11). A shorter DMFS for NM patients developing advanced disease compared with SSM patients was observed, while no difference was observed in the efficacy of systemic immunotherapy or BRAF/MEKi between NM and SSM patients. Our results suggests that the worse overall survival of NM is mainly driven by propensity of metastatic outgrowth of NM after primary diagnosis.
British journal of surgery · 2004 · 0 citations · open access
General 13–21
AbstractThe aim of this study was to review the outcome of sentinel lymph node biopsy (SLNB) in patients with melanoma and to identify the patients who developed nodal recurrence despite negative SLNB. Methods: Consecutive patients with cutaneous melanoma were identified from a prospective database between 1998 and 2003. Factors including demographic data, site, histological subtype, depth and outcome were examined. Results: Of 94 patients with a mean age of 52 (16-83) years 39 were male (41%). Primary melanoma sites included lower limb (48, 51%), upper limb (22, 24%), head (10, 11%), trunk (7, 7%) and back (7, 7%). The mean Breslow thickness was 28 mm. Superficial spreading accounted for 49% of melanoma subtypes with nodular accounting for 38%. SLNB identified at least one node in 93% of cases. On histopathology, 77% of nodes were negative. Mean follow-up was 27 (1-71) months. Of 19 relapses, 10 recurred in the same nodal basin, four recurred locally and five experienced haematogenous spread. Of the 10 patients who developed nodal recurrence, six (60%) had a negative sentinel node, three had positive sentinel nodes and one failed to map. Of the six patients with nodal recurrence despite a negative sentinel node, five (83%) were nodular melanoma histologically. The mean melanoma depth of these six patients was 246 (range, 151-360) mm. Conclusions: This study indicates that local recurrence occurs more often in SLNB-negative patients with nodular melanoma. Further evaluation of the inclusion criteria for sentinel mapping is warranted.
Journal of Clinical & Experimental Dermatology Research · 2021 · 0 citations
Nodular Melanoma what are the Threats and how to Treat this Disease
AbstractNodular Melanoma (NM) is the most aggressive form of melanoma. It tends to grow more rapidly in thickness(vertically penetrate the skin) than in diameter compared to other melanoma subtypes. Instead of arising from a pre-existing mole, it may appear in a spot where a lesion did not previously exist. Since NM tends to grow in depth morequickly than it does in width, and can occur in a place that did not have a previous lesion, the prognosis is oftenworse because it takes longer for a person to be aware of the changes.
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.
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