Novel Drug Discovery By Pharmacogenomic Profiling Of 36 Colorectal Cancer Cell Lines.

604 Background: Patients with advanced colorectal cancer (CRC) are commonly administered chemotherapy by 5-Fluorouracil in various combinations with leucovorin, oxaliplatin and irinotecan. Metastatic CRCs are additionally eligible for targeted anti-VEGF treatment and anti-EGFR therapy if the tumor is KRASwt. Unfortunately, the response rates are low and novel drugs are needed. Cell lines have successfully been employed to predict drug response and several studies have demonstrated that CRC cell lines recapitulate the genetic variation among primary CRCs. Methods: We performed a high-throughput drug screen (n= 461) of 36 CRC cell lines. A multiplexed assay assessed drug effects on cell viability and cytotoxicity from a five-fold concentration range. Sensitivities were measured by calculating a drug sensitivity score for each drug using a validated algorithm that estimates the relative inhibition by normalization against the top asymptote of the drug concentration curve. By integrating drug sensitivity data...