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Decoding the response to a PP2A inhibitor in pancreatic cancer

GSE300008 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2026/06/18 Platform GPL24247
Summary
The high failure rate of a cancer drug from target definition to clinical implementation highlights the need to prioritize context-specific targets. Here, we identify PP2A as an important target in pancreatic ductal adenocarcinoma (PDAC) by cancer-dependency scores. We characterized how inhibition of PP2A with the clinical grade inhibitor LB100 affects PDAC cells. Mesenchymal PDAC cells are highly susceptible to LB100-induced death. CRISPR-Cas9 drop-out screens revealed the contribution of the transcription cycle, splicing, or translation to the LB100 response. Mechanistically, PP2A inhibition disables the RNA polymerase II pause checkpoint, leading to CDK9-mediated transcriptional elongation linked to a ER stress response correlated with the formation of stress granules, autophagy, and cell death. We provide evidence for a PP2A inhibitor-sensitive subtype of PDAC and offer detailed insights into the cellular response induced by PP2A inhibitors.
Published in
The Protein Phosphatase Inhibitor LB100 Targets the Mesenchymal Lineage of Pancreatic Ductal Adenocarcinoma
Murr J, Schneider C, Duan N et al. · MedComm 2026 · PMID 42266180 · doi:10.1002/mco2.70794
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Also filed as BioProject PRJNA1278690 and SRA study SRP592622. Searching any of these in the dataset finder brings you back here.

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