Treatment with both MK2206 and L-buthionine-(S, R)-sulfoximine (BSO), which inhibit the EGFR effector AKT and glutathione synthase, respectively, mimicked the NRF2 depletion state and potently inhibited pancreatic cancer growth in KRAS- and TP53-mutated Suit2 PDA cell line and mouse models. Here, NFE2L2 is linked to familial pancreatic carcinoma.