ArticleThe Journal of clinical investigation2023
Peroxisome disruption alters lipid metabolism and potentiates antitumor response with MAPK-targeted therapy in melanoma.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Tissue-specific roles of peroxisomes revealed by expression meta-analysis.Biology direct · 2024Pooled it
- Integrated single-cell multiomics reveals neutrophil-driven immune-metabolic reprogramming of Kupffer cells via thrombospondin-1/CD36 after surgical stress.JCI insight · 2026Article
- MAPK Inhibitor-Tolerant Persister Cells in Melanoma: Mechanisms and Therapeutic Vulnerabilities.Cancer science · 2026Review
- Reciprocal signaling-metabolic crosstalk between fibroblasts and tumor cells drives cetuximab tolerance in head and neck cancers.Journal of experimental & clinical cancer research : CR · 2026Article
- Depression-induced systemic C16-ceramide deficiency promotes OSCC via attenuation of mitochondrial apoptosis.Cellular and molecular life sciences : CMLS · 2026Article
- Peroxisomal Lipid Metabolism as a Therapeutic Target in Leukemia.Molecular nutrition & food research · 2026Review
- Metabolic reprogramming-a breakthrough point in overcoming resistance to BRAF mutant melanoma targeted therapy (Review).Oncology letters · 2026Review
- Plasticity, signaling, and metabolic rewiring in melanoma persister cells.Communications biology · 2026Review
- Wastewater intelligence predicts the emergence of clinically-relevant and drug-resistant Candidozyma auris at healthcare facilities.Nature communications · 2026Article
- Uncovering the oncogenic role of RTTN in melanoma pathogenesis and its therapeutic implications.Molecular biology reports · 2026Article
- Metabolic reprogramming as a driver of immune escape in melanoma: implications for immunotherapy.Frontiers in immunology · 2026Review
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Peroxisomal fatty acid oxidation-related signature for predicting prognosis and therapeutic response in low-grade glioma.Frontiers in oncology · 2026Article
- Gut Microbiota-Derived Tyrosol Alleviates Radiation-Induced Intestinal Injury via Targeting SCD1-MUFA Axis to Suppress ER Stress.International journal of biological sciences · 2026Article
- Review
- Deciphering immune landscapes: an ICD-lncRNA-derived prognostic signature for pancreatic adenocarcinoma.Translational cancer research · 2025Article
- Central Roles of Glucosylceramide in Driving Cancer Pathogenesis.International journal of molecular sciences · 2025Review
- Peroxisomal lipid metabolism inhibits Pimozide-induced cancer cell death by regulating ATP homeostasis.Oncogenesis · 2025Article
- Transcriptome-wide decoding the roles of aberrant splicing in melanoma MAPK-targeted resistance evolution.EMBO reports · 2025Article
- Metabolic reprogramming in melanoma therapy.Cell death discovery · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Melanomas reprogram their metabolism to rapidly adapt to therapy-induced stress conditions, allowing them to persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKis) through a concerted metabolic reprogramming mediated by peroxisomes and UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, by repressing PEX3 expression, potentiated the proapoptotic effects of MAPKis via an induction of ceramides, an effect limited by UGCG-mediated ceramide metabolism. Cotargeting PEX3 and UGCG selectively eliminated a subset of metabolically active, drug-tolerant CD36+ melanoma persister cells, thereby sensitizing melanoma to MAPKis and delaying resistance. Increased levels of peroxisomal genes and UGCG were found in patient-derived MAPKi-relapsed melanomas, and simultaneously inhibiting PEX3 and UGCG restored MAPKi sensitivity in multiple models of therapy resistance. Finally, combination therapy consisting of a newly identified inhibitor of the PEX3-PEX19 interaction, a UGCG inhibitor, and MAPKis demonstrated potent antitumor activity in preclinical melanoma models, thus representing a promising approach for melanoma treatment.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.