Apoptosis is a highly regulated process critical for embryonic development, and tissue and organ homeostasis. Deregulation of apoptosis is a common occurrence in cancer. Emerging oncology therapeutic agents designed to engage apoptosis are currently undergoing clinical investigations. To identify unknown proteins that modulate the sensitivity to death receptor DR5 targeted agent drozitumab and to uncover predictive biomarkers, we perform a genome-wide screening of 18,000 genes by using pooled short hairpin RNA libraries, followed by the next generation sequencing for candidate identification. We have identified and confirmed candidate shRNA constructs and target genes that resulted in selective desensitizing of the cells to drozitumab. The roles and mechanisms of action of the newly identified proteins in modulating the extrinsic apoptotic pathway will be presented.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 254. doi:1538-7445.AM2012-254