Development of reverse phase protein microarrays for clinical applications and patient-tailored therapy.
While genomics provide important information about the somatic genetic changes, and RNA transcript profiling can reveal important expression changes that correlate with outcome and response to therapy, it is the proteins that do the work in the cell. At a functional level, derangements within the proteome, driven by post-translational and epigenetic modifications, such as phosphorylation, is the cause of a vast majority of human diseases. Cancer, for instance, is a manifestation of deranged cellular protein molecular networks and cell signaling pathways that are based on genetic changes at the DNA level. Importantly, the protein pathways contain the drug targets in signaling networks that govern overall cellular survival, proliferation, invasion and cell death. Consequently, the promise of proteomics resides in the ability to extend analysis beyond correlation to causality. A critical gap in the information knowledge base of molecular profiling is an understanding of the ongoing activity of protein signaling in human tissue: what is activated and "in use" within the human body at any given point in time. To address this gap, we have invented a new technology, called reverse phase protein microarrays, that can generate a functional read-out of cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. This "wiring diagram" can serve as the basis for both, selection of a therapy and patient stratification.
Speer
Runa
R
University of Tubingen, Faculty of Medicine, Department of Obstetrics and Gynecology, Calwer Str. 7, 72076 Tubingen, Germany, and Department of Surgery, Inova Fairfax Hospital Cancer Center, Falls Church, VA, USA.
Wulfkuhle
Julia
J
Espina
Virginia
V
Aurajo
Robyn
R
Edmiston
Kirsten H
KH
Liotta
Lance A
LA
Petricoin
Emanuel F
EF
D016923:Cell Death; D049109:Cell Proliferation; D002470:Cell Survival; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis / Q000639:trends; D010766:Phosphorylation; D040081:Protein Array Analysis / Q000639:trends; D011499:Protein Processing, Post-Translational; D012334:RNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm