SMAD4 and pancreatic neoplasm: In this study, we identified and characterized four nonisogenic colorectal and pancreatic cancer cell lines harboring wild-type (DLD1 and MIAPaCa-2) and mutant (HT29 and SW620) SMAD4, and we identified SMAD4-dependent genetic vulnerabilities through an unbiased, genome-wide, loss-of-function CRISPR/Cas9 screen (∼18,000 genes).