Pharmaco-Pheno-Multiomic Integration Builds a Biomarker Network of Olaparib Resistance in Ovarian Cancer

The overall survival of patients diagnosed with Ovarian Cancer remains low.  The current initial treatment regimen for patients with newly diagnosed advanced ovarian cancer includes the use of paclitaxel and carboplatin in combination with surgical cytoreduction.  Remission is often achieved, but 80% of patients will have a recurrence within 3 years of remission.  Recent treatment advances include the use of poly(ADP)-ribose polymerase (PARP) inhibitors for recurrent tumors with associated BRCA mutations. 

While maintenance treatment with PARP inhibitors results in remission for a significant number of patients, acquired resistance to therapy has been observed.  In this study, we evaluated biomarkers associated with resistance to the PARP inhibitor Olaparib in a cohort of platinum pretreated Ovarian Cancer tumors.  We identified Cyclin H and CDK7 expression, among others, as biomarkers associated with resistance to Olaparib.  Further prospective analyses confirmed CDK7 expression as a biomarker of resistance to Olaparib in NSCLC.