Several groups investigated allele-specific signaling in pancreatic cancer cell lines and organoids, and reported that, unlike KRAS G12D/V variants, G12R has a defective interaction with the key effector PI3K p110α, resulting in decreased PI3K-AKT-mTOR pathway signaling.16,22 In addition, KRAS G12R mutated cancers appeared more sensitive to MEK and PI3K inhibitors, preclinically.16,23. This evidence concerns the gene PIK3CA and familial pancreatic carcinoma.