The MUC1-HIF-1α signaling axis regulates pancreatic cancer pathogenesis through polyamine metabolism remodeling
Abstract
Pancreatic cancer is a devastating disease with limited treatment options and poor prognosis. This study uncovers a link between MUC1/hypoxia-inducible factor-1α (HIF-1α) signaling and polyamine metabolism. The study further highlights polyamine metabolism as a key survival pathway in tumor cells and demonstrates the utility of targeting polyamine metabolism in combination with FOLFIRINOX, the current standard of care therapy against advanced metastatic pancreatic ductal adenocarcinoma (PDAC). The combination of FOLFIRINOX with polyamine biosynthesis enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1) inhibitor pentamidine, an Food and Drug Administration (FDA)-approved broad-spectrum anti-infective agent active against several parasitic worms, protozoa, and fungi, showed significantly improved antitumor efficacy compared to FOLFIRINOX alone. Hence, this study can be readily translated into clinic and will form the basis of therapeutic combinations against PDAC.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2024
- DOI:
- 10.1073/pnas.2315509121
- Bibcode:
- 2024PNAS..12115509M