Clinical phosphoproteomic profiling for personalized targeted medicine using reverse phase protein microarray

Healthcare providers are increasingly incorporating information gleaned from genomics and proteomics in the diagnosis and treatment of cancer. These lines of inquiry are providing greater insight into why patients with similar histological tumor classification and staging often demonstrate dissimilar clinical outcomes, and are illuminating distinct diagnostic subgroups that are more responsive to specific treatment modalities. Clearer understanding of genes, gene products, and signaling pathways holds great promise for the personalization of molecular medicine. While the origins of oncologic disease are genetically encoded, the disease process is largely mediated through altered protein function. Recent investigations suggest that each individual patient's tumor possesses unique kinase-driven cell signaling derangements, and that these derangements derive, in part, from the tumor's relationship with its host microenvironment. Identification of signaling derangements and mapping functional protein-protein interactions via phosphoproteomic profiling offers great promise for the precise targeting of therapeutic agents, identifying new therapeutic targets, devising effective combinatorial therapies, monitoring treatment efficacy and toxicity, and ultimately predicting treatment outcome. This review focuses on advances in clinical phosphoproteomic profiling of cancer using the emerging technology of reverse phase protein microarrays, and highlights the translational roles this technology is playing in laying the foundations for personalized molecular therapeutics.