Responsive signatures established by pharmaco-transcriptomic correlation analysis identifies subsets for PARP-targeted therapy and reveals potential synergistic interactors

Abstract

Poly (ADP-ribose) polymerases (PARPs) have pleiotropic roles including canonical DNAdamage response pathways in tumors. Targeting PARP has gained increased attention to treat various cancer types. However, biomarkers predicting sensitivity/resistance to PARP inhibitors (PARPis) and cancer subtypes vulnerable to PARP targeted therapies remain to be defined. Through implementing integrative pharmaco-transcriptomic analyses by correlating the drug response profiles of clinicallyapproved PARPi Olaparib with the transcriptomes of solid cancer cell lines (n=659), we establish PARPis responsive gene signatures with high reproductivity. With the signatures, we identify tumor subsets vulnerable for PARPi and several potential targets synergistically interacting with PARPi.