Oncogenic KRAS supports pancreatic cancer through regulation of nucleotide synthesis

Abstract

Pancreatic ductal adenocarcinoma (PDAC) cells display varying degrees of reliance on oncogenic KRAS. Here the authors show that KRAS-resistant PDAC cells maintain nucleotides synthesis through a KRAS-independent upregulation of the non-oxidative pentose phosphate pathway gene RPIA and that targeting nucleotide metabolism restore sensitivity to KRAS pathway inhibition.