Pancreatic ductal adenocarcinoma (PDAC) is the most common and the deadliest form of pancreatic cancer, comprising 85% of all cases, with a five-year survival rate of just 6.7% [1, 2]. PDAC commonly arises from precancerous lesions called pancreatic intraepithelial neoplasias (PanINs) . These lesions are characterized by very high occurrence of mutations in the KRAS oncogene that are also maintained throughout disease progression and found in over 90% of PDAC cases . These findings indicate that KRAS could be a robust therapeutic target in PDAC. Indeed, murine pancreatic cancers with activated KRAS (e.g. KRASG12D and KRASG12V) exhibit oncogene addiction, whereby suppression of KRAS activity induces cell death in advanced tumors and regression of early PanINs [5–7]. However, efforts to directly inhibit KRAS activity in human tumors have thus far been unsuccessful . Moreover, clinical and preclinical studies have demonstrated the complexities of inhibiting the well-characterized downstream RAF/MEK/ERK and PI3K/AKT pathways [9–14]. These findings highlight the complexity of the signaling networks downstream of activated KRAS and suggest potential roles for post-transcriptional mechanisms that may buffer signaling downstream of KRAS. Therefore, a deeper understanding of the factors that influence KRAS-driven tumor initiation and progression in the pancreas is greatly needed.