DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for amelanotic skin melanoma — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAmelanotic skin melanoma maps to a 46-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 amelanotic skin 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
Amelanotic melanoma is a rare subtype that lacks visible pigment, making early diagnosis difficult. A 2018 case report describes a 72-year-old woman whose Clark’s level 4, 1.30 mm thick periorbital amelanotic melanoma was misdiagnosed as dermatitis for three years and required nine surgeries for resection. Delayed diagnosis is common in both amelanotic and melanotic melanoma and can be fatal; malignant melanoma accounts for up to 5% of cutaneous cancers but up to 75% of deaths from skin cancer.
For advanced melanoma generally, the solid tumour with the highest mutation burden, past chemotherapy showed no efficacy data. Recent progress has come from immunotherapies, targeted therapies, vaccines, small molecules, and combination therapies, which have shown promising effectiveness and safety in reviews. In BRAF-mutated metastatic melanoma, repeated use of BRAF/MEK inhibitors after an initial objective response and subsequent progression may offer clinical benefit, but resistance develops and questions remain about later treatment lines.
Drug repurposing for skin cancer is discussed in a 2021 mini-review as an alternative to developing novel medications, which can take 10–15 years and is expensive. Current therapies for melanoma still have disadvantages including little cell specificity, recurrent relapses, high toxicity, and increased costs. No repurposed drug candidate is named in any of these abstracts, and no trial data for any specific compound in amelanotic melanoma are provided.
What is still missing is any prospective trial designed specifically for amelanotic melanoma, which is too rare for large randomised studies without dedicated funding and multi-centre collaboration. Patient stratification by molecular subtype, including BRAF mutation status, is not addressed for the amelanotic form. No abstract reports survival or response rates for any drug in amelanotic melanoma.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Molecular Sciences · 2022 · 107 citations · open access
The Treatment of Advanced Melanoma: Therapeutic Update
AbstractCutaneous melanoma is the main cause of death for skin cancer. The majority of patients with a diagnosis of melanoma have localized disease, which can be successfully treated with surgical treatment. However, the surgical approach is not curative for advanced melanoma (AM). Indeed, the management of AM is still challenging, since melanoma is the solid tumor with the highest number of mutations and cancer cells have the capacity to evade the immune system. In the past, the treatment of AM relied on chemotherapeutic agents, without showing efficacy data. Recent knowledge on melanoma pathogenesis as well as the introduction of immunotherapies, targeted therapies vaccines, small molecules, and combination therapies has revolutionized AM management, showing promising results in terms of effectiveness and safety. The aim of this review is to assess and to discuss the role of emerging therapies for AM management in order to obtain a complete overview of the currently available treatment options and future perspectives.
BMJ Case Reports · 2018 · 53 citations · open access
Amelanotic melanoma: a unique case study and review of the literature
AbstractAmelanotic melanoma (AM) is a rare form of melanoma which lacks visible pigment. Due to the achromic manifestation of this atypical cutaneous malignancy, it has been difficult to establish clinical criteria for diagnosis. Thus, AM often progresses into an invasive disease due to delayed diagnosis. In this report, we describe the case of a 72-year-old Caucasian woman who had been diagnosed with AM after 3 years of failed treatments for what presented as a periorbital dermatitis. Her Clark's level 4, 1.30 mm thick melanoma required nine surgeries for successful resection and reconstruction. This case exemplifies the diagnostic pitfall of AM and the need for new criteria for early detection and management.
Advances in Dermatology and Allergology · 2019 · 26 citations · open access
Molecular background of skin melanoma development and progression: therapeutic implications
AbstractMelanoma is the most aggressive skin cancer with an increasing number of cases worldwide and curable mostly in its early stage. The improvement in patients' survival in advanced melanoma has been achieved only recently, due to development of new biological drugs for targeted therapies and immunotherapy. Further progress in the treatment of melanoma is clearly dependent on the better understanding of its complex biology. This review describes the most important molecular mechanisms and genetic events underlying skin melanoma development and progression, depicts the way of action of newly developed drugs and indicates new potential therapeutic targets.
Amelanotic melanoma presenting as contact dermatitis.
AbstractAuteur(s) : Asli Aksu Cerman1, Zeynep Demircay1, Cuyan Demirkesen2 1Department of Dermatology, Marmara University Faculty of Medicine, Istanbul, Turkey 2Department of Pathology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey Amelanotic melanoma is a rare form of melanoma. Because of the lack of pigmentation, this lesion is frequently misdiagnosed, as the clinical picture of amelanotic melanoma is so similar to that of inflammatory skin lesions. It [...]
Journal of the Dermatology Nurses’ Association · 2022 · 1 citations
Skin Cancer Back to Basics
AbstractABSTRACT Amelanotic melanoma is a rare subtype of cutaneous melanoma. Sun exposure is a known primary risk factor; however, the mechanism for amelanosis is poorly understood. Amelanotic melanoma is challenging to recognize clinically because of absence of pigment and its resemblance to a variety of benign and malignant neoplasms. Detection often occurs at late or metastatic stages, leading to poorer outcomes. Surgical excision is the current standard of care, with adjuvant therapies under investigation. This article discusses the clinical assessment and management of AM to improve early recognition and patient outcomes.
International Journal of Pathology and Clinical Research · 2018 · 0 citations · open access
Malignant Melanoma Arising of Gland Pigmentary Disorders
AbstractMalignant melanoma represents up to 5% of cutaneous cancers, but up to 75% of the cases have fatal outcomes. The early diagnosis and prompt treatment can reduce the impressive mortality rate of this ominous malignancy. Both amelanotic and melanotic melanoma may be associated with delayed clinical suspicion and late diagnosis, harmful occurrence that may be related to lack of awareness of health care workers or unusual site of the tumors.
Greater South Information System · 2021 · 0 citations · open access
Repurposing of Drug Candidates for Treatment of Skin Cancer
AbstractSkin cancers are highly prevalent malignancies that affect millions of people worldwide. These include melanomas and nonmelanoma skin cancers. Melanomas are among the most dangerous cancers, while nonmelanoma skin cancers generally exhibit a more benign clinical pattern; however, they may sometimes be aggressive and metastatic. Melanomas typically appear in body regions exposed to the sun, although they may also appear in areas that do not usually get sun exposure. Thus, their development is multifactorial, comprising endogenous and exogenous risk factors. The management of skin cancer depends on the type; it is usually based on surgery, chemotherapy, immunotherapy, and targeted therapy. In this respect, oncological treatments have demonstrated some progress in the last years; however, current therapies still present various disadvantages such as little cell specificity, recurrent relapses, high toxicity, and increased costs. Furthermore, the pursuit of novel medications is expensive, and the authorization for their clinical utilization may take 10–15 years. Thus, repositioning of drugs previously approved and utilized for other diseases has emerged as an excellent alternative. In this mini-review, we aimed to provide an updated overview of drugs' repurposing to treat skin cancer and discuss future perspectives.
Effective Pharmacotherapy · 2023 · 0 citations · open access
Repeated Use of BRAF and MEK Inhibitors in Patients with BRAF-Mutated Metastatic Melanoma of the Skin
AbstractIn this paper we review the existing data and our clinical experience of repeated use of combination therapy with BRAF/MEK inhibitors (BRAFi/MEKi) in the treatment of patients with BRAF-mutated metastatic melanoma of the skin. Recent advances in medical oncology significantly increased the life expectancy of patients with metastatic and/or unresectable melanoma of the skin. However, some patients develop resistance to therapy. Retreatment after interruption or "intermediate" therapy may be of clinical benefit. Contemporary drug therapy becomes more available and there are fewer challenges to chose the first and second line therapy for patients with metastatic and/or unresectable melanoma, but there are still questions on subsequent treatment options when BRAFi/MEKi therapy had been used after the disease progression following the initial objective response. In this article, we review the definitions of “retreatment” or “rechallenge”, give the overview of the literature data, and present our clinical experience
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.
