ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Proteomic Analysis of CSF from Patients with Leptomeningeal Melanoma Metastases Identifies Signatures Associated with Disease Progression and Therapeutic Resistance.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 57 citations in OpenAlex.
- GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma.Cancer research · 2026Article
- Integrated Proteomic and Metabolomic Analyses of Cerebrospinal Fluid from Pediatric Patients with Diffuse Intrinsic Pontine Glioma.International journal of molecular sciences · 2026Article
- Outcomes and prognostic factors in melanoma patients with leptomeningeal disease: a retrospective cohort study.Melanoma research · 2026Article
- Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review).Oncology letters · 2026Review
- Melanoma leptomeningeal disease: Advances in diagnosis and emerging therapeutic strategies.World journal of experimental medicine · 2026Review
- The Leptomeningeal Microenvironment in Metastasis: A Unique Central Nervous System Niche.Annals of Indian Academy of Neurology · 2026Article
- Article
- Beyond the brain: exploring the impact of animal models of leptomeningeal disease from solid tumors.Acta neuropathologica communications · 2025Review
- Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasis.Scientific reports · 2025Article
- Cerebral spinal fluid analyses and therapeutic implications for leptomeningeal metastatic disease.Journal of neuro-oncology · 2025Review
- Leptomeningeal metastatic disease: new frontiers and future directions.Nature reviews. Clinical oncology · 2025Review
- Deep Proteome Analysis of Cerebrospinal Fluid from Pediatric Patients with Central Nervous System Cancer.Journal of proteome research · 2024Article
- Leptomeningeal metastases from solid tumors: A Society for Neuro-Oncology and American Society of Clinical Oncology consensus review on clinical management and future directions.Neuro-oncology · 2024Review
- Survival and treatment outcomes in patients with leptomeningeal disease from metastatic melanoma.Neuro-oncology practice · 2024Article
- The path to leptomeningeal metastasis.Nature reviews. Cancer · 2024Review
- Spatial transcriptomics analysis identifies a tumor-promoting function of the meningeal stroma in melanoma leptomeningeal disease.Cell reports. Medicine · 2024Article
- Review
- Leptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care.Pigment cell & melanoma research · 2024Review
- Spatial transcriptomics analysis identifies a unique tumor-promoting function of the meningeal stroma in melanoma leptomeningeal disease.bioRxiv : the preprint server for biology · 2023Article
- Branched-chain keto acids promote an immune-suppressive and neurodegenerative microenvironment in leptomeningeal disease.bioRxiv : the preprint server for biology · 2023Article
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10 authors at 1 institution in 1 country.
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Abstract
purposeThe development of leptomeningeal melanoma metastases (LMM) is a rare and devastating complication of the late-stage disease, for which no effective treatments exist. Here, we performed a multi-omics analysis of the cerebrospinal fluid (CSF) from patients with LMM to determine how the leptomeningeal microenvironment shapes the biology and therapeutic responses of melanoma cells. EXPERIMENTAL
designA total of 45 serial CSF samples were collected from 16 patients, 8 of these with confirmed LMM. Of those with LMM, 7 had poor survival (<4 months) and one was an extraordinary responder (still alive with survival >35 months). CSF samples were analyzed by mass spectrometry and incubated with melanoma cells that were subjected to RNA sequencing (RNA-seq) analysis. Functional assays were performed to validate the pathways identified.
resultsMass spectrometry analyses showed the CSF of most patients with LMM to be enriched for pathways involved in innate immunity, protease-mediated damage, and IGF-related signaling. All of these were anticorrelated in the extraordinary responder. RNA-seq analysis showed CSF to induce PI3K/AKT, integrin, B-cell activation, S-phase entry, TNFR2, TGFβ, and oxidative stress responses in the melanoma cells. ELISA assays confirmed that TGFβ expression increased in the CSF of patients progressing with LMM. CSF from poorly responding patients conferred tolerance to BRAF inhibitor therapy in apoptosis assays.
conclusionsThese analyses identified proteomic/transcriptional signatures in the CSF of patients who succumbed to LMM. We further showed that the CSF from patients with LMM has the potential to modulate BRAF inhibitor responses and may contribute to drug resistance.
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