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<p>High-grade pancreatic neuroendocrine carcinoma (panNEC) is a rare, aggressive cancer with limited tissue availability. Single-nucleus transcriptomics of five large-cell panNECs revealed two clinically relevant neuroendocrine cell states: one highly proliferative with an aberrant brain-specific neuronal differentiation program and another stress-responsive state enriched for heat stress, hypoxia, and glycolysis. Our findings suggest potential therapeutic vulnerabilities, highlighting the need to evaluate the efficacy of combination therapies.</p>

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Aberrant brain-type neuronal programs in large-cell pancreatic neuroendocrine carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月30日

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  • Olivia Debnath,
  • Hilmar Berger,
  • Katharina Detjen,
  • Philipp Kirchner,
  • Ilaria Marinoni,
  • Ines Eichhorn,
  • Felix Bolduan,
  • Thomas Conrad,
  • David Horst,
  • Roland Eils,
  • Bertram Wiedenmann,
  • Aurel Perren,
  • Naveed Ishaque

摘要

High-grade pancreatic neuroendocrine carcinoma (panNEC) is a rare, aggressive cancer with limited tissue availability. Single-nucleus transcriptomics of five large-cell panNECs revealed two clinically relevant neuroendocrine cell states: one highly proliferative with an aberrant brain-specific neuronal differentiation program and another stress-responsive state enriched for heat stress, hypoxia, and glycolysis. Our findings suggest potential therapeutic vulnerabilities, highlighting the need to evaluate the efficacy of combination therapies.