Adverse Drug Events-based Tumor Stratification for Ovarian Cancer Patients Receiving Platinum Therapy

AMIA Jt Summits Transl Sci Proc. 2015 Mar 23:2015:51-5. eCollection 2015.

Abstract

The underlying molecular mechanisms of adverse drug events (ADEs) associated with cancer therapy drugs may overlap with their antineoplastic mechanisms. In a previous study, we developed an ADE-based tumor stratification framework (known as ADEStrata) with a case study of breast cancer patients receiving aromatase inhibitors, and demonstrated that the prediction of per-patient ADE propensity simultaneously identifies high-risk patients experiencing poor outcomes. In this study, we aim to evaluate the ADEStrata framework with a different tumor type and chemotherapy class - ovarian cancer treated with platinum chemotherapeutic drugs. We identified a cohort of ovarian cancer patients receiving cisplatin (a standard platinum therapy) from The Cancer Genome Atlas (TCGA) (n=156). We demonstrated that somatic variant prioritization guided by known ADEs associated with cisplatin could be used to stratify patients treated with cisplatin and uncover tumor subtypes with different clinical outcomes.