Abstract SY08-02: Markers of caspase activation in cells and serum

Abstract

Abstract The final and hoped for outcome for treatment with cancer drugs is selective apoptosis of cancer cells. However, despite the low response rates to cancer drugs patients do not discover this until months after treatment has begun. Apoptosis is rapid process which is often induced within 24 hours of drug treatment. The hallmark of apoptosis is the activation of caspases, cysteine proteases that are specific for cleaving target proteins after aspartic acid. We have developed a novel proteomics technology that allows us to tag and enrich for caspase-cleaved proteins during apoptosis (Mahrus et al (2008) Cell, 134, 866-876. “Global Sequencing of Proteolytic Cleavage Sites in Apoptosis by Specific Labeling of Protein N Termini”). We have been characterizing the apoptotic products of caspase cleavage in a variety of cell lines and in human serum with the view that this information can be used to monitor apoptosis during cancer drug treatment. These and other studies in a variety of cancer cell lines showed that upwards of 1000 proteins are cleaved by caspases during apoptosis. However, in any given cell line we find there are fewer than 500 targets because of differences in expression patterns between cell types. Thus, while many targets are in common from one cell line to another, many are unique. We have developed single-reaction monitoring (SRM) methods to identify these products in serum. We are beginning to identify specific apoptotic products in leukemia patients treated with various cancer drugs. These studies and the prospects for using these as apoptotic markers to assist in cancer drug treatment will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY08-02. doi:10.1158/1538-7445.AM2011-SY08-02