Adaptation to an acid microenvironment promotes pancreatic cancer organoid growth and drug resistance [drug]

We investigated transcriptomic changes in PanIN ("mP4") mouse pancreatic ductal organoids under acute or long-term treatment of Gemcitabine and Erlotinib. The mP4 organoids were gradually adapted to growth in medium containing 10 nM of drugs (Erlotinib, Gemcitabine or combination), by increasing drug concentrations by 1 nM / week over a period of 12 weeks. As controls, we kept organoids at 0 nM drug concentrations for the same time. A subset of control organoids were acutely treated with 10 nM erlotinib, gemcitabine or the combination of the two at 12 weeks. Expression prolifing analysis was conducted based on RNAseq of 33 samples from 2 experiments: drug adaptation experiment (24 samples from week 1 and 12), and acute drug treatment experiment (9 samples).