Sensitization of pancreatic cancer to chemoradiation by the Chk1 inhibitor MK8776.

ABSTRACT:

Purpose

The combination of radiation with chemotherapy is the most effective therapy for unresectable pancreatic cancer. To improve upon this regimen, we combined the selective Checkpoint kinase 1 (Chk1) inhibitor MK8776 with gemcitabine-based chemoradiation in preclinical pancreatic cancer models.

Experimental design

We tested the ability of MK8776 to sensitize to gemcitabine-radiation in homologous recombination repair (HRR)-proficient and -deficient pancreatic cancer cells and assessed Rad51 focus formation. In vivo, we investigated the efficacy, tumor cell selectivity, and pharmacodynamic biomarkers of sensitization by MK8776.

Results

We found that MK8776 significantly sensitized HRR-proficient (AsPC-1, MiaPaCa-2, BxPC-3) but not -deficient (Capan-1) pancreatic ca

SUBMITTER: Engelke CG 

PROVIDER: S-EPMC3745540 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature