Network analysis of immunotherapy-induced regressing tumours identifies novel synergistic drug combinations.

ABSTRACT: Cancer immunotherapy has shown impressive results, but most patients do not respond. We hypothesized that the effector response in the tumour could be visualized as a complex network of interacting gene products and that by mapping this network we could predict effective pharmacological interventions. Here, we provide proof of concept for the validity of this approach in a murine mesothelioma model, which displays a dichotomous response to anti-CTLA4 immune checkpoint blockade. Network analysis of gene expression profiling data from responding versus non-responding tumours was employed to identify modules associated with response. Targeting the modules via selective modulation of hub genes or alternatively by using repurposed pharmaceuticals selected on the basis of their expression pertur

SUBMITTER: Lesterhuis WJ 

PROVIDER: S-EPMC4508665 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature