Clinical proteomics for cancer biomarker discovery and therapeutic targeting.
As we emerge into the post-genome era, proteomics finds itself as the driving force field as we translate the nucleic acid information archive into understanding how the cell actually works and how disease processes operate. Even so, the traditionally held view of proteomics as simply cataloging and developing lists of the cellular protein repertoire of a cell are now changing, especially in the sub-discipline of clinical proteomics. The most relevant information archive to clinical applications and drug development involves the elucidation of the information flow of the cell; the "software" of protein pathway networks and circuitry. The deranged circuitry of the cell as the drug target itself as well as the effect of the drug on not just the target, but also the entire network, is what we now are striving towards. Clinical proteomics, as a new and most exciting sub-discipline of proteomics, involves the bench-to-bedside clinical application of proteomic tools. Unlike the genome, there are potentially thousands of proteomes: each cell type has its own unique proteome. Moreover, each cell type can alter its proteome depending on the unique tissue microenvironment in which it resides, giving rise to multiple permutations of a single proteome. Since there is no polymerase chain reaction equivalent to proteomics- identifying and discovering the "wiring diagram" of a human diseased cell in a biopsy specimen remains a daunting challenge. New micro-proteomic technologies are being and still need to be developed to drill down into the proteomes of clinically relevant material. Cancer, as a model disease, provides a fertile environment to study the application of proteomics at the bedside. The promise of clinical proteomics and the new technologies that are developed is that we will detect cancer earlier through discovery of biomarkers, we will discover the next generation of targets and imaging biomarkers, and we can then apply this knowledge to patient-tailored therapy.
Krieg
Rene C
RC
FDA-NCI Clinical Proteomics Program, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Paweletz
Cloud P
CP
Liotta
Lance A
LA
Petricoin
Emanuel F
EF
D000465:Algorithms; D014408:Biomarkers, Tumor; D001706:Biopsy; D019295:Computational Biology; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007834:Lasers; D013058:Mass Spectrometry / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D040081:Protein Array Analysis / Q000379:methods*; D020543:Proteome
D014408:Biomarkers, Tumor; D020543:Proteome