Aberrant brain-type neuronal programs in large-cell pancreatic neuroendocrine carcinoma
Olivia DebnathiD, Hilmar BergeriD, Katharina M Detjen, Philipp KirchneriD, Ilaria MarinoniiD, Ines Eichhorn, Felix BolduaniD, Thomas ConradiD, David A. HorstiD, Roland EilsiD, Bertram J. WiedenmanniD, Aurel A. PerreniD, Naveed IshaqueiD
Abstract
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 potentially new therapeutic vulnerabilities, highlighting the need to evaluate the efficacy of combination therapies.
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