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Reverse phase protein microarrays for theranostics and patient-tailored therapy
Virginia Espina1, Julia Wulfkuhle, Valerie S Calvert
1Laboratory of Pathology, National Cancer Institute, Center for Cancer Research, Bethesda, MD, USA.
Methods in Molecular Biology (Clifton, N.J.)
|March 29, 2008
Summary
Proteomics reveals how protein networks drive disease, offering causal insights beyond genomics. Reverse phase protein microarrays map patient-specific cell signaling pathways for targeted cancer therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Proteins, not just genes, are key drivers of cellular functions and disease processes.
- Diseases like cancer involve disrupted protein networks and cell-signaling pathways with numerous drug targets.
- Proteomics offers insights into molecular causality, moving beyond genomic correlations.
Purpose of the Study:
- To introduce reverse phase protein microarrays (RPPA) for mapping cellular signaling pathways.
- To demonstrate the clinical utility of RPPA in generating patient-specific functional pathway maps.
- To highlight the potential of RPPA for identifying drug targets and guiding personalized therapy.
Main Methods:
- Development and application of reverse phase protein microarrays (RPPA).
- Immobilization of the entire cellular proteome onto a substratum.
- Immunodetection of phosphorylated (activated) signaling proteins from biopsy specimens.
Main Results:
- RPPA generates a functional map of cell-signaling networks for individual patients.
- This map identifies critical nodes and pathways involved in disease.
- Quantification of protein phosphorylation states reveals pathway activity.
Conclusions:
- RPPA technology provides a patient-specific "circuit diagram" of cellular signaling.
- This "theranostic" approach can guide individualized or combinatorial drug therapies.
- RPPA serves as a diagnostic and therapeutic guide by correlating pathway activity with clinical information.
Related Concept Videos
02:34DNA Microarrays
Microarrays are high-throughput and relatively inexpensive assays that can be automated to analyze large quantities of data at a time. They are used in genome-wide studies to compare gene or protein expression under two varied conditions, such as healthy and diseased states. Microarrays consist of glass or silica slides on which probe molecules are covalently attached through surface functionalization. Most commonly, the slides are prepared through the chemisorption of silanes to silica...
01:33Proteomics
A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term proteomics...
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term proteomics...