Reverse-Phase Protein Microarrays for Theranostics and Patient Tailored Therapy

Analysis of the genome provides important information about the somatic genetic changes existing in the tissue; however, it is the proteins that do the work of the cell. Diseases such as cancer are caused by derangements in cellular protein molecular networks and cell signaling pathways. These pathways contain a large and growing collection drug targets, governing cellular survival, proliferation, invasion, and cell death. The clinical utility of reverse-phase protein microarrays (RPPA), a new technology invented in our laboratory, lies in its ability to generate a functional map of known cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. Coupled with laser capture microdissection (LCM), the RPPA platform, the entire cellular proteome is immobilized on a substratum with subsequent immunodetection of the total levels and phosphorylated, or activated, state of cell signaling proteins. The results of which pathways are “in use” can then be correlated with biological and clinical information and serve as both a diagnostic and a therapeutic guide, thus providing a “theranostic” endpoint.