(342a) Drugsea: A Bioinformatic Tool to Identify Classes of Drugs with Differential Sensitivity

There is a pressing need for targeted therapies in diseases such as cancer. While targeted therapies have the potential for efficacy with minimal effects on normal tissues, it is estimated that only seven to eight percent of cancer patients are candidates for targeted therapies. To facilitate the identification of drugs which may bear therapeutic benefit for patients with particular genotypes or phenotypes, we present Drug Set Enrichment Analysis (drugSEA). drugSEA is an algorithm which analyzes drug sensitivity data from 1,351 drugs profiled on 327 cancer cell lines to identify drug targets that are differentially sensitive for individual genotypes or phenotypes. We first tested and validated our approach using synthetic data. Next, we further validated our method using published datasets to recapitulate known drug sensitivities towards EGFR, PI3K, and HDAC inhibitors. Finally, we used drugSEA to identify novel drugs which exhibit sensitivity in cancer cell lines based on their RNA expression of cystine/glutamate antiporter, xCT. Collectively, this study presents drugSEA as a bioinformatic tool which can identify drug targets with differential sensitivity towards individual genotypes or phenotypes.