Caspase-8 activation by TRAIL monotherapy predicts responses to IAPi and TRAIL combination treatment in breast cancer cell lines.

ABSTRACT: The discovery of cancer cell-selective tumour necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis generated broad excitement and development of TRAIL receptor agonists (TRA) as potential cancer therapy. Studies demonstrating the synergistic combination effect of SMAC mimetics and TRA further suggested potentially effective treatment in multiple tumour settings. However, predictive biomarkers allowing identification of patients that could respond to treatment are lacking. Here, we described a high throughput combination screen conducted across a panel of 31 breast cancer cell lines in which we observed highly synergistic activity between TRAIL and the inhibitors of apoptosis proteins (IAP) inhibitor (IAPi) AZD5582 in ~30% of cell lines. We detected no difference in t

SUBMITTER: Polanski R 

PROVIDER: S-EPMC4632282 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature