SHH and pancreatic ductal adenocarcinoma: Aberrant Sonic Hedgehog (Shh) expression occurs in early benign pancreatic precursor lesions, contributing to progressive changes in pancreatic stroma.1 Shh-mediated stromal remodeling contributes to poor response rates in patients undergoing standard-of-care therapies,2,3 suggesting that targeting mechanisms that restrict Shh release might prevent progression to pancreatic ductal adenocarcinoma (PDAC) by reducing the stromal therapeutic barrier.