EP300 and cancer: To investigate whether the resistance to PORCN inhibitors observed in RNF43-mutant pancreatic cancer cell lines (Supplemental Figure 1A) was due to loss of p300, we first used the Cancer Cell Line Encyclopedia (CCLE; ref. 23) gene-expression database to analyze the transcript levels of both EP300 and CREBBP in a cohort of pancreatic cancer cell lines (Figure 3A).