Aberrant brain-type neuronal programs in large-cell pancreatic neuroendocrine carcinoma
Debnath, O.; Berger, H.; Detjen, K.; Kirchner, P.; Marinoni, I.; Eichhorn, I.; Bolduan, F.; Conrad, T.; Horst, D.; Eils, R.; Wiedenmann, B.; Perren, A.; Ishaque, N.
Show 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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