The polymeric fluoropyrimidine CF10 overcomes limitations of 5-FU in pancreatic ductal adenocarcinoma cells through increased replication stress.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease soon to become the second leading cause of cancer deaths in the US. Beside surgery, current therapies have narrow clinical benefits with systemic toxicities. FOLFIRINOX is the current standard of care, one component of which is 5- Fluorouracil (5-FU), which causes serious gastrointestinal and hematopoietic toxicities and is vulnerable to resistance mechanisms. Recently, we have developed polymeric fluoropyrimidines (F10, CF10) which unlike 5-FU, are, in principle, completely converted to the thymidylate synthase inhibitory metabolite FdUMP, without generating appreciable levels of ribonucleotides that cause systemic toxicities while displaying much stronger anti-cancer activity. Here, we confirm the potency of CF10 and investigate

SUBMITTER: Finan JM 

PROVIDER: S-EPMC11552260 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature