Targeted protein quantification by selected reaction monitoring (SRM) on tandem mass spectrometers is rapidly becoming an essential technique for investigation and monitoring of complex signaling pathways and biological processes. In cancer biology, the information it can provide can have direct implications for patient assessment, including assessment of drug resistance and metastasis. Informed by existing knowledge of cancer biology and prior experiments in gene expression profiling, assays can be developed to measure hypothesis-driven protein targets in tumor cells. As examples, NF-kB survival signaling, apoptosis-related proteins in the Bcl-2 family, and DNA damage response elements are measured in models of acquired drug resistance in multiple myeloma. Assays targeting b-catenin signaling have been successfully translated into frozen colon tissue sections and laser capture microdissected tumor cells to examine tumor biology in situ. Dr. Koomen's presentation will discuss these and other examples, exploring the development of targeted protein assays based on existing knowledge and research. It will also focus on translation of methods from preliminary screens performed on cell lines to assays for patient specimens. |