Targeting PIKfyve-driven lipid metabolism in pancreatic cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) subsists in a nutrient-deregulated microenvironment, making it particularly susceptible to treatments that interfere with cancer metabolism^1,2. For example, PDAC uses, and is dependent on, high levels of autophagy and other lysosomal processes^3-5. Although targeting these pathways has shown potential in preclinical studies, progress has been hampered by the difficulty in identifying and characterizing favourable targets for drug development⁶. Here, we characterize PIKfyve, a lipid kinase that is integral to lysosomal functioning⁷, as a targetable vulnerability in PDAC. Using a genetically engineered mouse model, we established that PIKfyve is essential to PDAC progression. Furthermore, through comprehensive

SUBMITTER: Cheng C 

PROVIDER: S-EPMC12176661 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature