DeCure for Melanoma and neural system tumor syndrome
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for melanoma and neural system tumor syndrome — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMelanoma and neural system tumor syndrome maps to a 1-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 melanoma and neural system tumor syndrome 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.
What the evidence adds up to
Melanoma central nervous system metastases are common and carry a poor prognosis. A study of patients diagnosed between 1986 and 2004, before effective systemic therapy was available, reported a median overall survival of as little as 4.7 months. Most clinical trials exclude patients with intracranial metastases. Localised therapies such as surgery and stereotactic radiotherapy are applicable only to a minority of patients. Immunotherapy has shown clinical benefit compared with best supportive care, and when given alongside radiotherapy it provides better overall survival than radiotherapy alone.
BRAF inhibitors have demonstrated efficacy in active brain metastases in BRAF-mutated melanoma. The CTLA-4 antibody ipilimumab has shown activity, particularly in asymptomatic metastases. Studies of PD-1/PD-L1 checkpoint inhibitors and combination BRAF and MEK inhibitor therapy in brain metastases were planned as of 2014. Emerging evidence on the phosphatidylinositol 3-kinase-AKT pathway may identify additional therapeutic targets. More research is required in patients with active brain metastases, including studies early in the development of novel therapies and studies to determine safe and effective combination or sequencing of local and systemic therapies.
In a preclinical study using human neural stem cells as drug delivery vehicles, a cell line expressing cytosine deaminase and human interferon-β was tested on melanoma cells. In the presence of the prodrug, the engineered stem cells prevented malignant melanoma cells from proliferating in vitro and in xenograft mouse models. The secreted interferon-β modified the epithelial-mesenchymal transition process and metastasis. The authors concluded that neural stem cell-directed enzyme/prodrug therapy is a plausible treatment for malignant melanoma, but no human data are available.
For the rare entity of central nervous system meningeal melanocytomas, a National Cancer Database study identified 143 patients diagnosed between 2004 and 2017. The median age at diagnosis was 59 years. Gross total resection was reported in 28 patients (19.6%), and adjuvant radiotherapy was given to 51 patients (35.7%). The 1-year and 5-year overall survival rates were approximately 80% and 50%, respectively. There were no significant differences in overall survival based on sex, age, tumour location, extent of resection, or use of adjuvant radiotherapy. The authors concluded that the optimal management of CNS melanocytomas remains an area of ongoing investigation and that future prospective studies should focus on refining treatment indications. What is still missing for melanoma CNS metastases are prospective trials that include patients with active brain metastases, studies that determine how to sequence or combine local and systemic therapies, and human data for the stem-cell delivery approach. For melanocytomas, the evidence base lacks prospective studies and any stratification that might identify which patients benefit from surgery or radiotherapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Pigment Cell & Melanoma Research · 2016 · 149 citations · open access
Melanoma central nervous system metastases: current approaches, challenges, and opportunities
AbstractIn February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper, we outline the current status of basic science, translational, and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area.
AbstractBrain metastases occur commonly in patients with metastatic melanoma, are associated with a poor prognosis, and cause significant morbidity. Both surgery and stereotactic radiosurgery are used to control brain metastases and, in selected patients, improve survival. In those with extensive brain involvement, whole-brain radiotherapy can alleviate symptoms. Historically, systemic therapy has had little role to play in the management of melanoma brain metastases; however, early clinical trials of BRAF inhibitors have shown promising activity. This review examines the evidence for local and systemic treatments in the management of patients with melanoma brain metastases. We present a new treatment algorithm for melanoma patients with brain metastases, which integrates the evolving evidence for the use of BRAF inhibitors.
Clinical Cancer Research · 2018 · 38 citations · open access
Rates of<i>ERBB2</i>Alterations across Melanoma Subtypes and a Complete Response to Trastuzumab Emtansine in an<i>ERBB2</i>-Amplified Acral Melanoma
AbstractAbstract Purpose: Patients with BRAF V600 wild-type melanoma whose tumors progress on checkpoint inhibition currently have limited therapeutic options, and additional rational treatment targets are needed. ERBB2 alterations may be amenable to targeted inhibition, but the rate of ERBB2 alterations across melanoma subtypes is not well described. Patients and Methods: All patients with nonuveal melanoma (cutaneous, acral, mucosal, and unknown primary) whose tumors underwent multigene sequencing with MSK-IMPACT at Memorial Sloan Kettering Cancer Center (New York, NY) from 2014 to 2018 were reviewed for known or likely oncogenic somatic alterations in ERBB2 and the other known canonical driver genes BRAF, NRAS, KIT, NF1, GNAQ, and GNA11. Results: A patient with acral melanoma resistant to checkpoint inhibition was found to have ERBB2 amplification and achieved a durable complete response to trastuzumab emtansine. Tumor sequencing results from 732 melanoma cases were analyzed for ERBB2 and canonical driver gene alterations. ERBB2 amplifications were detected in acral (3%) and mucosal (3%) melanomas. ERBB2 mutations were found in cutaneous (1%), acral (2%), and mucosal (2%) subtypes and frequently cooccurred with NF1 alterations. Among the 140 patients whose tumors lacked canonical driver alterations, ERBB2 amplifications were detected in acral (7%) and mucosal (6%) melanomas. Conclusions: ERBB2 amplification is present in a minority of acral lentiginous and mucosal melanomas. Activating mutations in ERBB2 were identified in nonuveal melanoma subtypes and are frequently comutated with canonical drivers. HER2 could represent a therapeutically relevant target across melanoma subtypes.
The role of systemic therapies in the management of melanoma brain metastases
AbstractPURPOSE OF REVIEW: Brain metastases in metastatic melanoma are highly prevalent and are associated with significant morbidity and a poor prognosis. Local therapy (surgery or radiotherapy) has been the mainstay of treatment, due in part to the lack of efficacy of systemic therapy. This review will focus on new systemic therapies for metastatic melanoma and their evolving role in the management of brain metastases. RECENT FINDINGS: BRAF inhibitors have demonstrated efficacy in active (i.e. untreated or progressing) brain metastases in BRAF mutated metastatic melanoma. The cytotoxic T lymphocyte antigen 4 (CTLA-4) antibody, ipilimumab, has also shown activity, particularly in asymptomatic metastases. Studies of programmed death 1/programmed death ligand 1 checkpoint inhibitors and combination BRAF and MEK inhibitor therapy in brain metastases are planned. Emerging evidence on the molecular biology of melanoma brain metastases, particularly the role of the phosphatidylinositol 3-kinase-AKT pathway, may identify additional therapeutic targets. SUMMARY: The development of systemic therapy effective in controlling both intra-cranial and extra-cranial melanoma metastases has resulted in a change in the paradigm of management. More research is required in patients with active brain metastases to improve patient outcomes, including studies early in the development of novel therapies, and studies to determine the safe and effective combination or sequencing of local and systemic therapies.
Cancer Research and Treatment · 2018 · 11 citations · open access
A Potential Therapy Using Engineered Stem Cells Prevented Malignant Melanoma in Cellular and Xenograft Mouse Models
AbstractPURPOSE: In the present study, human neural stem cells (hNSCs) with tumor-tropic behavior were used as drug delivery vehicle to selectively target melanoma. A hNSC line (HB1.F3) was transduced into two types: one expressed only the cytosine deaminase (CD) gene (HB1.F3. CD) and the other expressed both CD and human interferon-β (IFN-β) genes (HB1.F3.CD. IFN-β). MATERIALS AND METHODS: This study verified the tumor-tropic migratory competence of engineered hNSCs on melanoma (A375SM) using a modified Boyden chamber assay in vitro and CM-DiI staining in vivo. The antitumor effect of HB1.F3.CD and HB1.F3.CD.IFN-β on melanoma was also confirmed using an MTT assay in vitro and xenograft mouse models. RESULTS: A secreted form of IFN-β from the HB1.F3.CD.IFN-β cells modified the epithelial-mesenchymal transition (EMT) process and metastasis of melanoma. 5-Fluorouracil treatment also accelerated the expression of the pro-apoptotic protein BAX and decelerated the expression of the anti-apoptotic protein Bcl-xL on melanoma cell line. CONCLUSION: Our results illustrate that engineered hNSCs prevented malignant melanoma cells from proliferating in the presence of the prodrug, and the form that secreted IFN-β intervened in the EMT process and melanoma metastasis. Hence, neural stem cell-directed enzyme/prodrug therapy is a plausible treatment for malignant melanoma.
Melanoma central nervous system metastases: current approaches, challenges, and opportunities
AbstractMelanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here, we provide a review of the current status of the field of melanoma brain metastasis research; identify key challenges and opportunities for improving the outcomes in patients with melanoma brain metastases; and set a framework to optimize future research in this critical area.
IntechOpen eBooks · 2022 · 0 citations · open access
Intracranial Metastatic Melanoma
AbstractCentral nervous system (CNS) metastases are a common manifestation of malignant melanoma, with a median overall survival of as little as 4.7 months based on a study of patients diagnosed between 1986 and 2004 prior to the era of effective systemic therapy. Yet most of the clinical trials exclude patients with intra-cranial metastases. CNS involvement often causes neurological deficits and functional impairment. Localised therapies, such as surgical excision and stereotactic radiotherapy are applicable to only a minority of patients. There are evidences of clinical benefits for immunotherapy than best supportive care and when given alongside radiotherapy provides a better overall survival than radiotherapy alone. This chapter evaluates the efficacy and toxicity of these treatments against advanced melanoma patients with brain metastases.
Brain and Spine · 2025 · 0 citations · open access
Overall survival following treatment of central nervous system meningeal melanocytomas: Insights from the national cancer database (NCDB)
AbstractIntroduction: Central nervous system (CNS) melanocytomas are rare, pigmented tumors derived from leptomeningeal melanocytes. Although generally benign, they can exhibit locally aggressive behavior and recur. Despite increasing recognition, data on their clinical outcomes and optimal management remain limited. Research question: This study aimed to evaluate the survival outcomes of patients with CNS melanocytomas, using a large national registry, and to explore the prognostic relevance of tumor location and treatment modalities. Methods: We queried the National Cancer Database (NCDB) for cases of CNS melanocytomas diagnosed between 2004 and 2017. Patient demographics, tumor characteristics, treatment details, and survival outcomes were collected. Kaplan-Meier survival analysis was used to study overall survival (OS). Results: A total of 143 patients with CNS melanocytomas were identified, including 58 spinal (40.6 %), 49 intracranial (34.3 %), 36 tumors of unspecified location (25.2 %). The median age at diagnosis was 59 years, with males comprising 48.3 % of the cohort. Gross total resection (GTR) was reported in 28 patients (19.6 %), while adjuvant radiotherapy was performed in 51 patients (35.7 %). The 1- and 5-year OS rates were approximately 80 % and 50 %, respectively. There were no significant differences in OS based on sex, age, tumor location, extent of resection, or use of adjuvant radiotherapy (p ≥ 0.05). Discussion and conclusion: Despite advances in surgical techniques and radiation therapy, the optimal management of CNS melanocytomas remains an area of ongoing investigation. Since our findings failed to demonstrate a survival benefit from GTR or the use of adjuvant radiotherapy, future prospective studies should focus on refining treatment indications.
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.
