Resected pancreatic cancer treated pre-operatively with chemotherapy is enriched for cells that co-express GATA6, KRT17 and CYP3A. Persistent expression of GATA6hi and KRT17hi is associated with poor survival after treatment with mFOLFIRINOX, but not gemcitabine. CYP3A-expressing drug detoxification pathways metabolize the prodrug irinotecan, a constituent of mFOLFIRINOX, leading to persistent drug tolerance.
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References
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This is a summary of: Zhou, X. et al. Persister cell phenotypes contribute to poor patient outcomes after neoadjuvant chemotherapy in PDAC. Nat. Cancer https://doi.org/10.1038/s43018-023-00628-6 (2023).
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Neoadjuvant chemotherapy enriches for drug-tolerant persisters in PDAC. Nat Cancer 4, 1226–1227 (2023). https://doi.org/10.1038/s43018-023-00629-5
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DOI: https://doi.org/10.1038/s43018-023-00629-5
