RNAi Validation of Pancreatic Cancer Antigens Identified by Cell Surface Proteomics

摘要: Pancreatic cancer is one of the most aggressive malignancies that often diagnosed at a late stage following tumor metastasis. Given low response rate to current therapies, there clear and urgent need for new therapeutic diagnostic approaches. Proteomics an emerging tool offers opportunity discover novel antigens elevated in cancer. Considering large number marketed drugs target plasma membrane proteins, given their amenability both small molecule antibody-based technologies, approach combines cell labeling strategy with proteomic (LC-MS/MS) methodology would enable surface can act as biomarkers and/or targets drug development be identified. One major consideration when selecting therapeutics whether or not antigen plays functional role disease context. RNA interference (RNAi) permits downregulation any gene, therefore allows identification functionality disease. As such, this selection prior investment antibody program extensive molecule–screening program. In chapter, we describe utility LC-MS/MS method was developed Celera. Subsequent application RNAi allowed us assign identified were upregulated pancreatic By using combination proteomics platform, demonstrate it possible devastating