PPARG and adenocarcinoma: Although these mutations have been classified as “very rare events” [70, 71], increasing evidence suggests that PPARγ activity is attenuated during the transition from adenoma to adenocarcinoma, likely explaining why PPARγ agonists are effective in blocking the early stages of tumorigenesis (i.e., ACF formation is inhibited while little or no effect is detected in advanced tumor stages) [71–74].