Pilot clinical trial of hedgehog pathway inhibitor GDC-0449 (vismodegib) in combination with gemcitabine in patients with metastatic pancreatic adenocarcinoma.

ABSTRACT:

Purpose

The hedgehog (HH) signaling pathway is a key regulator in tumorigenesis of pancreatic adenocarcinoma and is upregulated in pancreatic adenocarcinoma cancer stem cells (CSCs). GDC-0449 is an oral small-molecule inhibitor of the HH pathway. This study assessed the effect of GDC-0449-mediated HH inhibition in paired biopsies, followed by combined treatment with gemcitabine, in patients with metastatic pancreatic adenocarcinoma.

Experimental design

Twenty-five patients were enrolled of which 23 underwent core biopsies at baseline and following 3 weeks of GDC-0449. On day 29, 23 patients started weekly gemcitabine while continuing GDC-0449. We evaluated GLI1 and PTCH1 inhibition, change in CSCs, Ki-67, fibrosis, and assessed tumor response, survival and toxicity.

Resul

SUBMITTER: Kim EJ 

PROVIDER: S-EPMC4254161 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature