Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer.

ABSTRACT: There is a need to develop effective therapies for pancreatic ductal adenocarcinoma (PDA), a highly lethal malignancy with increasing incidence¹ and poor prognosis². Although targeting tumour metabolism has been the focus of intense investigation for more than a decade, tumour metabolic plasticity and high risk of toxicity have limited this anticancer strategy^3,4. Here we use genetic and pharmacological approaches in human and mouse in vitro and in vivo models to show that PDA has a distinct dependence on de novo ornithine synthesis from glutamine. We find that this process, which is mediated through ornithine aminotransferase (OAT), supports polyamine synthesis and is required for tumour growth. This directional OAT activity is usually largely restricted t

SUBMITTER: Lee MS 

PROVIDER: S-EPMC10929664 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature