A Central Role for RAF-MEK-ERK Signaling in the Genesis and Maintenance of Pancreatic Ductal Adenocarcinoma.

ABSTRACT: Although KRAS mutation is a hallmark of pancreatic ductal adenocarcinoma (PDA), mutated KRAS remains an intractable pharmacological target. Consequently, an understanding of the RAS effector pathway(s) required for PDA maintenance is critical for improved strategies to treat this disease. Here we demonstrate that expression of BRAFV600E, but not PIK3CAH1047R, in the mouse pancreas led to PanIn lesions. Moreover, concomitant expression of BRAFV600E and TP53R270H resulted in lethal PDA. A large panel of PDA cell line panel was deployed to derive genomic classifiers of MEK inhibitor sensitivity. This classifier correctly predicted survival benefit in two novel in vivo syngeneic, orthotopic models of PDA. Consequently, we conclude that RAF?MEK?ERK signaling is central to the initiation, p

ORGANISM(S): Mus musculus

SUBMITTER: Christopher Szeto 

PROVIDER: E-GEOD-30562 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress