We also found that de novo lipid synthesis was driven by the KRAS–MAPK pathway and, accordingly, therapeutic inhibition of both PIKfyve and KRAS–MAPK signalling resulted in sustained tumour regression or elimination in multiple mouse models of PDAC, including the Pft1a-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ (KPC) autochthonous model. Here, KRAS is linked to neoplasm.