DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Anal 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 moduleAnal 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 anal 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
Anal melanoma remains rare and prognosis is poor. A population-based study of 160 patients treated between 1982 and 2002 found median survival was similar whether patients had local excision (28 months) or rectal resection (17 months), a difference that was not statistically significant (P = .3). Even after pathological staging, five-year survival for rectal resection patients with localised disease was 43.1% versus 12.5% for regional disease (P = .17), and survival after rectal resection was no better than after local excision for either stage. The authors concluded that extent of surgery does not appear to change survival.
A later analysis of 815 patients from the National Cancer Database covering 2004 to 2020 showed a shift in practice: between 2013 and 2020 fewer abdominoperineal resections were performed (18% versus 28%, P = .002) and more local excisions (61.1% versus 55%, P = .002). Immunotherapy use increased (odds ratio 3.41, P < .001) and chemotherapy use decreased (odds ratio 0.516, P < .001). Median overall survival improved from 19.8 months in 2004–2012 to 25.2 months in 2013–2020 (P = .006). Independent predictors of worse survival were older age (hazard ratio 1.02, P = .012), higher Charlson comorbidity score (hazard ratio 2.32, P = .02), and a greater number of positive lymph nodes (hazard ratio 1.15, P < .001); private insurance was associated with better survival (hazard ratio 0.385, P = .008).
Sex differences were examined in a separate NCDB analysis of 1,467 patients (594 male, 873 female) diagnosed between 2005 and 2022. Mean overall survival was shorter for males (48.35 months) than for females (59.41 months, P < .01). After multivariable adjustment, male sex remained an independent predictor of worse survival (hazard ratio 1.240, 95% CI 1.087–1.416, P < .01). Landmark survival rates at three years were 33.8% for males versus 40.0% for females (P = .02), and at five years 23.0% versus 28.4% (P = .02). Overall mortality was 70.88% in males and 66.55% in females (P = .09).
What is still missing is prospective data that can separate the effect of newer systemic therapies from the shift toward less radical surgery, and any trial that randomises between treatment strategies. The sex difference is unexplained and no mechanism is established. Patient stratification by molecular subtype or immune profile is not yet standard, and no drug repurposing candidate has been tested in a controlled trial for this disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Diseases of the Colon & Rectum · 2010 · 59 citations
Long-term Outcomes After Local Excision and Radical Surgery for Anal Melanoma: Data From a Population Database
AbstractPURPOSE: Anal melanoma is rare and associated with a poor outcome. Previous studies that have reported outcomes after surgical treatment are limited by both small number of participants and treatment at single centers only. This study evaluates survival of patients undergoing surgery for anal melanoma from a prospective, population-based database. METHODS: Characteristics and survival of patients undergoing rectal resection or local excision for anal melanoma of the anus, anal canal, and overlapping region of the rectum from 1982 to 2002 were obtained from the Surveillance, Epidemiology and End Results database and compared. RESULTS: A total of 160 patients were included in the study. Details of previous surgical procedures were available for 109 of the study patients: 60 (55%) underwent local excision and 49 (45%) rectal resection. Patients who underwent local excision were significantly older (73.5 vs 65.1 years, P < .001), whereas those who had undergone rectal resection had a greater proportion of regional disease (73.5% vs 16.7%, P < .001). The median survival of the 2 groups was similar (rectal resection vs local excision: 17 vs 28 months, P = .3). Rectal resection and local excision were associated with similar survival for patients in both regional (P = .6) and localized (P = .95) stages. Outcomes for patients who were appropriately pathologically staged after rectal resection depended on localized vs regional stage (5-year survival: 43.1% vs 12.5%, P = .17). Survival for patients in localized and regional stages who underwent rectal resection was similar to that for patients with corresponding clinical stage who underwent local excision. CONCLUSION: Survival of patients with anal melanoma is similar after local excision or rectal resection irrespective of whether patients have localized or regional stage of disease.
World Journal of Oncology · 2015 · 4 citations · open access
Anorectal Melanoma: A Case Report and an Update of a Rare Malignancy
AbstractAnal melanoma is an aggressive but rare malignancy. Patients commonly present with very advanced or even metastatic disease. Risk factors for anal melanoma are family history and an activating mutation of C-KIT. Surgical excision remains the mainstay of therapy. The presence of activating mutations of C-KIT has prompted use of C-KIT inhibitors such as imatinib and sunitini. Early diagnosis and treatment remain crucial. Abdominal perineal resection (APR) offers a higher rate of local control whereas wide local excision (WLE) can yield superior long-term survival.
A national database analysis of the evolution of outcomes of surgery for anal melanoma
AbstractBACKGROUND: This study assessed trends in treatment and outcomes of anal melanomas over a 17-year period. METHODS: NCDB was searched for patients with anal melanoma (2004-2020). Receiver-operating characteristic curve analysis was used to determine cutoff year marking increased overall survival (OS) of anal melanoma. Characteristics, treatments, and outcomes in consecutive time periods were compared. RESULTS: A total of 815 patients (mean age: 67.2 years; 59.4% female) were included: 354 in Period 1 (2004-2012) and 461 in Period 2 (2013-2020). Period 2 included fewer abdominoperineal resections (18% vs. 28%, p = 0.002), more local tumor excisions (61.1% vs. 55%, p = 0.002), more often immunotherapy (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 2.22-5.22, p < 0.001) and less often chemotherapy (OR: 0.516, 95% CI: 0.352-0.755, p < 0.001) administered and longer median OS (25.2 vs. 19.8 months, p = 0.006). Independent predictors of worse OS were older age (hazard ratio [HR]: 1.02, p = 0.012), higher Charlson score (HR: 2.32, p = 0.02), and greater number of positive lymph nodes (HR: 1.15, p < 0.001); conversely private insurance (HR: 0.385, p = 0.008) was predictive of increased OS. CONCLUSIONS: Anal melanoma patients diagnosed between 2013 and 2020 underwent fewer abdominoperineal resections and more local excisions than patients diagnosed between 2004 and 2013. Increased immunotherapy and longer median OS were noted in period two. Age and private insurance were significant predictors of OS, remaining constant across time periods.
Sex differences in survival of anal melanoma: An analysis of the United States National Cancer Database.
Abstracte21607 Background: Mucosal melanoma is a rare, more aggressive subtype of melanoma, accounting for < 2% of all melanomas and associated with a poorer prognosis than cutaneous malignant melanomas. It can occur in any part of the body that contains melanocytes, including anywhere along the gastrointestinal tract with the anorectal region being the most common location. Patients with anorectal melanoma typically present with late-stage disease and treatment options are not well established given the rarity of the disease. Although sex differences in survival have been observed for cutaneous melanomas, with females having a survival advantage over males, sex differences in survival have not been well established in anal melanoma. This study aimed to compare the survival outcomes of anal melanoma between male and female patients using a national registry from the United States. Methods: Adult patients who were diagnosed with anal melanoma were identified from the National Cancer Database (NCDB) of Anal Cancer from 2005 to 2022 based on ICDO-3 codes. Patients undergoing palliative care were excluded. Overall survival (OS) was analyzed using Kaplan-Meier (KM) plots, log-rank tests, and Cox proportional hazard models that controlled for age, race and ethnicity, primary payor, income, education, facility type/location, comorbidities, treatment, and TNM staging. Results: Among the patients with anal melanoma, 594 were males and 873 were females. Males had a shorter mean OS (p < 0.01; Table). KM curves of the two groups were created, and a log-rank test showed a statistically significant difference in survival rates (p = 0.04). After multivariable analysis, OS remained significantly lower in male patients (HR 1.240, 95 CI 1.087-1.416, p < 0.01). Landmark survival rates of males were lower than that of females at 3 years [0.338 (95 CI 0.299-0.380) vs 0.400 (95 CI 0.366-0.435), p = 0.02] and 5 years [0.230 (95 CI 0.194-0.269) vs 0.284 (95 CI 0.250-0.319), p = 0.02] (Table). Conclusions: Males with anal melanoma exhibit worse survival outcomes compared to females, which is consistent with the known survival differences in cutaneous melanoma. Further research is needed to investigate the underlying mechanisms behind these differences and to develop targeted treatment strategies. Overall mortality, mean survival time, and landmark survival rates between male and female patients with anal melanoma. Male(n = 594) Female(n = 873) p-value Overall mortality (n, %) 421 (70.88%) 581 (66.55%) 0.09 Survival month (mean ± SE) 48.35 ± 2.73 59.41 ± 2.71 <0.01 Landmark survival rates (%, 95 CI) 6-month 0.883 (0.853-0.907) 0.885 (0.861-0.905) 0.91 1-year 0.734 (0.695-0.769) 0.744 (0.711-0.771) 0.67 2-year 0.501 (0.458-0.543) 0.511 (0.475-0.545) 0.71 3-year 0.338 (0.299-0.38) 0.400 (0.366-0.435) 0.02 5-year 0.230 (0.194-0.269) 0.284 (0.366-0.435) 0.02 Abbreviations: CI, confidence interval; SE, standard error.
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.
