1413-LSD1-GLS2 Drives Subtype-Specific Chemoresistance

Paper Talk · Aug 10, 2026 · 24m

This research identifies lysine-specific demethylase 1 (LSD1) as a pivotal metabolic regulator that dictates how pancreatic cancer cells respond to chemotherapy based on their molecular subtype. The study demonstrates that inhibiting LSD1 sensitizes RSK-subtype cells, which rely on healthy mitochondrial respiration, while paradoxically inducing resistance in KRAS-subtype cells characterized by mitochondrial dysfunction and defective mitophagy. Mechanistically, LSD1 represses the enzyme GLS2, acting as a transcriptional switch that governs glutamine metabolism. In RSK-subtype tumors, this axis…