Issues

Carrer and colleagues observed that the enzyme ATP-citrate lyase (ACLY) increases production of acetyl-CoA and promotes acinar-ductal metaplasia (ADM) and tumorigenesis in Kras-mutant pancreatic cells through increased acetyl-coA availability for histone acetylation and the mevalonate pathway. This in turn renders PDAC sensitive to inhibitors of the BET family of proteins, which recognize acetylated histones, and statins, which target the mevalonate pathway. These findings suggest that acetyl-coA plays key metabolic and signaling roles in PDAC and that targeting acetyl-coA–dependent processes may be a potential therapeutic strategy. For details, please see the article by Carrer and colleagues on page 416.