Hedgehog inhibition prolongs survival in a genetically engineered mouse model of pancreatic cancer.

ABSTRACT:

Background and aims

Pancreatic cancer is among the most dismal of human malignancies. Current therapeutic strategies are virtually ineffective in controlling advanced, metastatic disease. Recent evidence suggests that the Hedgehog signalling pathway is aberrantly reactivated in the majority of pancreatic cancers, and that Hedgehog blockade has the potential to prevent disease progression and metastatic spread.

Methods

Here it is shown that the Hedgehog pathway is activated in the Pdx1-Cre;LsL-Kras(G12D);Ink4a/Arf(lox/lox) transgenic mouse model of pancreatic cancer. The effect of Hedgehog pathway inhibition on survival was determined by continuous application of the small molecule cyclopamine, a smoothened antagonist. Microarray analysis was performed on non-malignant human

SUBMITTER: Feldmann G 

PROVIDER: S-EPMC2707354 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature