FGFR2 Abrogation Intercepts Pancreatic Ductal Adenocarcinoma Development.

ABSTRACT: Activating KRAS mutations are a key feature of pancreatic ductal adenocarcinoma (PDAC) and drive tumor initiation and progression. However, mutant KRAS by itself is weakly oncogenic. Defining the pathways that cooperate with mutant KRAS to induce tumorigenesis could identify prevention and treatment strategies. Analyzing organoids and murine and human pancreatic specimens, we found that the receptor tyrosine kinase FGFR2 was progressively upregulated in mutant KRAS-driven metaplasia, precancerous lesions, and classical PDAC. In genetic mouse models, FGFR2 inactivation impeded mutant KRAS-driven transformation of acinar cells by reducing proliferation and MAPK pathway activation. FGFR2 abrogation significantly delayed tumor formation and extended the survival of these mice. Furthermore, FGF

SUBMITTER: Tonelli C 

PROVIDER: S-EPMC12169444 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature