The differential response to AZD6244 observed in KPC KrasG12D/fl and KPC KrasG12D/+ tumors further supports the hypothesis that loss of the WT Kras allele profoundly affects the oncogenic signaling within pancreatic tumors and that the presence of a WT Kras allele can contribute to therapeutic resistance in Kras mutant tumors. Here, KRAS is linked to pancreatic neoplasm.