KRAS inhibition activates an actionable CD24 'don't eat me' signal in pancreas cancer.

Lack of faithful preclinical models limits the exploration of resistance mechanisms to KRAS inhibitor in PDAC. We generated an autochthonous KRAS -driven PDAC model, which revealed allele-specific biology of the KRAS during PDAC development. We identified CD24 as an actionable adaptive mechanisms in cancer cells induced upon KRAS inhibition and blocking CD24 sensitizes PDAC to KRAS inhibitors in preclinical models.