Reverse phase protein microarrays for monitoring biological responses.

Abstract

Cancer has a genomic and proteomic basis. Genomic information provides information about the somatic genetic changes existing in the tumor that provides a survival advantage driving neoplastic progression. On the other hand, proteomics aids in the identification of dysregulated cellular proteins, including known or novel drug targets, governing cellular survival, proliferation, invasion, and cell death. The clinical utility of reverse phase protein microarrays lies in their ability to generate a map of known cell signaling networks or pathways for an individual patient. This protein network map aids in identifying critical nodes or pathways that may serve as drug targets for individualized or combinatorial therapy. Reverse phase protein microarrays are one of the tools available for profiling the protein molecular pathways in a given cellular sample. This type of microarray can uniquely quantify phosphorylation states of proteins. An entire cellular proteome is immobilized on a substratum with subsequent immunodetection of total and activated forms of cell signaling proteins. The pattern of signal intensity generated by the protein spots can be correlated with biological and clinical information as diagnostic and prognostic indicators.