We identify PI3K activation as a common molecular pathway activated by increased consumption of red and processed meat and by inflammatory condition to promote pancreatic plasticity and precancer lesion development.

As we show that treatments with the clinically available PI3Kα inhibitor block pancreatic plasticity under inflammatory stress while maintaining pancreas mass and limiting inflammatory reaction damage, they may represent an efficient and safe preventive interception drug in patients at risk of developing pancreatic cancer. PI3K pro-cancer action is exacerbated by the loss of serine synthesis enzyme; hence, diets that alter amino acid synthesis should be tightly controlled in those patients.