DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for acral lentiginous melanoma — screening already-approved drugs against its 48-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAcral lentiginous melanoma maps to a 48-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
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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 acral lentiginous 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
Acral lentiginous melanoma is an uncommon subtype of cutaneous melanoma that arises on the palms, soles, and nail unit. In a 1995 retrospective review of 56 patients, the average age at diagnosis was 61.1 years; 61% were white and 39% were African-American, Hispanic, or Asian. Forty-three percent of primary tumours were thicker than 4.00 mm. When corrected for tumour thickness, disease-free and overall survival did not differ between acral lentiginous melanoma and other histologic subtypes, and only thickness was an independent prognostic variable.
A 2021 multi-centre analysis of 433 primary acral lentiginous melanoma patients (median age 66 years, 53% female, 83% white) reported 5-year melanoma-specific survival by stage as: stage 0 = 100%, stage I = 93.8%, stage II = 76.2%, stage III = 63.4%, stage IIIA = 80.8%, and stage IV = 0%. Thicker Breslow depth (HR 1.13, 95% CI 1.05–1.21) and positive nodal status (HR 1.79, 95% CI 1.00–3.22) were independent prognostic factors for melanoma-specific survival. The authors noted that stage IIB and IIC disease carried particularly low survival and recurrence-free survival, and suggested that adjuvant therapy trials in stage II patients might be especially valuable for this subtype.
A 2021 systematic review of treatment for metastatic acral lentiginous melanoma found only three studies meeting inclusion criteria, with no phase 3 clinical trials and high heterogeneity across a total of 63 patients. In one study, dasatinib yielded a median overall survival of 21.1 months and progression-free survival of 2.8 months. A second study reported 3-year overall survival of 28.7% with nivolumab. An observational study comparing three treatment classes reported: chemotherapy median overall survival 8.3 months and progression-free survival 2.1 months; immunotherapy median overall survival 16.6 months and progression-free survival 11.4 months; targeted therapy median overall survival 21.7 months and progression-free survival 11.4 months. The review concluded that worldwide there is no good-quality scientific information to define the best specific treatment for metastatic acral lentiginous melanoma.
What is still missing are adequately powered prospective trials, including phase 3 randomised designs, that are specific to acral lentiginous melanoma rather than extrapolated from other melanoma subtypes. The disease’s UV-independent biology and distinct genomic drivers remain poorly characterised, and no validated biomarkers exist to stratify patients for targeted or immunotherapy approaches. Funding for dedicated multi-centre studies, particularly in populations where acral lentiginous melanoma is the most common subtype, 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.
Archives of Surgery · 1995 · 77 citations
Acral Lentiginous Melanoma
AbstractOBJECTIVE: To analyze whether the histologic subtype acral lentiginous melanoma confers independent prognostic significance. DESIGN: Case series retrospective review. SETTING: Academic surgical practice. PATIENTS OR OTHER PARTICIPANTS: Fifty-six patients with histologically confirmed acral lentiginous melanoma identified from patients with malignant melanoma consecutively treated by the faculty of the Department of Surgical Oncology at the University of Illinois at Chicago. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lymph node metastases, disease-free survival, and overall concurrent or subsequent survival. RESULTS: The average age of our patients with acral lentiginous melanoma was 61.1 years. Thirty-four (61%) were white, and the remaining 22 (39%) were African-American, Hispanic, or Asian. Thirty (54%) were male and 26 (46%) were female. The primary tumor occurred on the lower extremity in 46 (82%) of the cases and on the upper extremity in the remaining 10 (18%). Twenty-four primary tumors (43%) were greater than 4.00 mm thick. Analyzed by means of a logistic regression model, the rate of lymph node metastases did not significantly differ among patients with acral lentiginous melanoma, superficial spreading melanoma, and nodular malignant melanoma. Furthermore, when corrected for tumor thickness, disease-free and overall survival were the same for the three histologic groups. Multifactorial analysis identified only thickness as a prognostic variable for disease-free survival and overall survival. CONCLUSIONS: Despite the greater age, diverse ethnic background, and distinctive tumor characteristics of our patients with acral lentiginous melanoma, this histologic subtype does not, in itself, affect the outcome of these patients.
Cancer Control · 2021 · 32 citations · open access
Acral Lentiginous Melanoma: A United States Multi-Center Substage Survival Analysis
AbstractBackground Acral lentiginous melanoma is associated with worse survival than other subtypes of melanoma. Understanding prognostic factors for survival and recurrence can help better inform follow-up care. Objectives To analyze the clinicopathologic features, melanoma-specific survival, and recurrence-free survival by substage in a large, multi-institutional cohort of primary acral lentiginous melanoma patients. Methods Retrospective review of the United States Melanoma Consortium database, a multi-center prospectively collected database of acral lentiginous melanoma patients treated between January 2000 and December 2017. Results Of the 433 primary acral lentiginous melanoma patients identified (median [range] age: 66 [8–97] years; 53% female, 83% white), 66% presented with stage 0–2 disease and the median time of follow-up for the 392 patients included in the survival analysis was 32.5 months (range: 0–259). The 5-year melanoma-specific survivals by stage were 0 = 100%, I = 93.8%, II = 76.2%, III = 63.4%, IIIA = 80.8%, and IV = 0%. Thicker Breslow depth ((HR) = 1.13; 95% CI = 1.05–1.21; P < .001)) and positive nodal status ((HR) = 1.79; 95% CI = 1.00–3.22; P = .050)) were independent prognostic factors for melanoma-specific survival. Breslow depth ((HR = 1.13; 95% CI = 1.07–1.20; P < .001), and positive nodal status (HR = 2.12; 95% CI = 1.38–3.80; P = .001) were also prognostic factors for recurrence-free survival. Conclusion In this cohort of patients, acral lentiginous melanoma was associated with poor outcomes even in early stage disease, consistent with prior reports. Stage IIB and IIC disease were associated with particularly low melanoma-specific and recurrence-free survival. This suggests that studies investigating adjuvant therapies in stage II patients may be especially valuable in acral lentiginous melanoma patients.
AbstractWe present a rare case of a patient with multiple primary acral lentiginous melanomas of the foot. We would like to highlight the importance of whole-skin examination in all patients, even by the general practitioners, aiming the maximal early detection of acral lentiginous melanomas, considering their rapid progression, early metastatic spread and extremely poor prognosis. It can be extrapolated from current literature; however, that appropriate management of these patients, including staging work and surgical intervention, is to be determined by the individual characteristics of the melanoma and the patient's concomitant risk factors, if any.
Treatment of metastatic acral lentiginous melanoma: Systematic review.
Abstracte21536 Background: Acral lentiginous melanoma (AML) is infrequent malignant melanoma subtype (5%) .It does not have specific treatment. The objective of this article is to summarize the best available evidence regarding the specific treatment of metastatic acral lentiginous melanoma. Methods: A systematic review of the literature was proposed. A search was carried out in the databases of Pubmed, Embase, Scopus, Lilacs in English and Spanish, during the last 20 years. The equation used was ((“acral lentiginous melanoma”) AND (“Treatment”)). For quality assessment, the JAMA guidelines for qualifying and globally through the GRADE system, the Cochrane guideline for evaluation of clinical trial bias was used. The review process involved 3 researchers and differents filters for evaluating the scientific evidence. The primary outcome was overall survival (OSm) and progression-free survival (PFS) as a secondary outcome. Results: 208 articles were found, only 3 articles were included. No phase 3 clinical trial. The summary of the data and qualification of evidence are in Table. In total there were 63 patients. It was found high heterogeneity in the 3 studies. The outcomes were those reported directly from each study, a subgroup analysis was not required. In first study, overall survival 21.1m was found with Dasatinib and PFS 2.8m. The second clinical trial, found OS with Nivolumab of 28.7% at 3 years. The last study was observational, and included three different treatment options, the outcomes were: Chemotherapy OSm 8.3m and PFS 2.1m, Immunotherapy OSm 16.6m and PFS 11.4m and Targeted therapy OSm 21.7m and PFS 11.4m. Conclusions: Worldwide, there is no good quality scientific information to define the best specific treatment for acral lentiginous melanoma. Current available evidence suggests that treatment with targeted therapies such as c-kit, V600E or immunotherapy as some useful options. Link Prospero: CRD42020171528.[Table: see text]
Greater South Information System · 2020 · 0 citations · open access
Acral lentiginous melanoma: Basic facts, biological characteristics and research perspectives of an understudied disease
AbstractAcral lentiginous melanoma is a histological subtype of cutaneous melanoma that occurs in the glabrous skin of the palms, soles and the nail unit. Although in some countries, particularly in Latin America, Africa and Asia, it represents the most frequently diagnosed subtype of the disease, it only represents a small proportion of melanoma cases in European-descent populations, which is partially why it has not been studied to the same extent as other forms of melanoma. As a result, its unique genomic drivers remain comparatively poorly explored, as well as its causes, with current evidence supporting a UV-independent path to tumorigenesis. In this review, we discuss current knowledge of the aetiology and diagnostic criteria of acral lentiginous melanoma, as well as its epidemiological and histopathological characteristics. We also describe what is known about the genomic landscape of this disease and review the available biological models to explore potential therapeutic targets.
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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