ArticleJCO oncology advances2025
Molecular Characterization and Clinical Outcomes of Pancreatic Neuroendocrine Neoplasms Harboring PAK4-NAMPT Alterations.
Article in JCO oncology advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Aerobic glycolysis-driven lactate accumulation and acidic tumor microenvironment in hepatocellular carcinoma: a vicious cycle promoting tumor progression.Frontiers in pharmacology · 2026Review
- Article
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Authors and funding
27 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe mammalian target of rapamycin (mTOR) inhibitor everolimus is US Food and Drug Administration-approved for advanced pancreatic neuroendocrine neoplasms (pNENs), yet resistance is common, necessitating the identification of resistance mechanisms for effective treatment strategies. Previous studies suggest that targeting the aberrant expression of mTOR regulators p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyl transferase (NAMPT) sensitizes pNENs to everolimus. In this study, we queried a large real-world data set of pNENs, characterizing the molecular and immune landscapes, as well as the clinical outcomes associated with aberrant PAK4 and NAMPT expression.
methodsTwo-hundred and ninety-four pNEN cases were analyzed using next-generation sequencing and whole-exome/whole-transcriptome sequencing. We stratified patients into clusters on the basis of median cutoff.
resultsHigh expression of genes activated in response to mTOR activation was found in NAMPT-high and PAK4-high groups. Enrichment of PI3K/AKT/mTOR and glycolysis pathways was observed in these tumors. Higher mutation rates in multiple endocrine neoplasia type 1, alpha thalassemia/mental retardation syndrome X-linked, TSC2, SETD2, and CCNE1 were observed in high NAMPT and PAK4 clusters. Immune analysis revealed enrichment in inflammatory response pathways, IL2/STAT5 signaling, and immune checkpoint genes. Increased neutrophils, natural killer cells, and macrophages were found in PAK4-high/NAMPT-high tumors. Analysis of real-world patient data revealed that high PAK4 (
conclusionOur study demonstrates that PAK4-high/NAMPT-high pNENs are associated with distinct molecular and immune profiles. Further investigation is warranted to determine if dual PAK4 and NAMPT blockade enhances the efficacy of immunotherapeutics.
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Registered trials
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