Mining the tumor phosphoproteome for cancer markers

Despite decades of cancer research, mortality rates remain high largely due to the failure of early detection, poor understanding of the epidemiology of rational drug targets, and molecular etiology of human cancers. The discovery of disease markers promises to deliver some solutions to these formidable challenges. Gene and protein expression profiling through DNA microarray and proteomics have already made a tremendous effect in this area. However, protein/gene expression does not necessarily reflect protein activity, which is often regulated via post-translation modifications, of which phosphorylation is one of the most prominent. This is an important consideration because the activity of protein is a more relevant phenotype than its expression during pathogenesis. Tyrosine kinases represent a very important class of enzymes that are critical regulators of mitogenic and angiogenic signaling, hence attractive targets for anticancer drugs as exemplified by BCR-ABL and ErbB2. More than 50% of them are overexpressed or mutated resulting in a gain of function in various human cancers. In this review, we discuss the potential effect of phosphoproteins as cancer markers in cancer diagnosis and therapeutics. Phosphoproteomics strategies that might pave the way to high-throughput analysis for routine clinical applications are also described.