Proteomic approaches to the diagnosis, treatment, and monitoring of cancer.
The field of proteomics holds promise for the discovery of new biomarkers for the early detection and diagnosis of disease, molecular targets for therapy and markers for therapeutic efficacy and toxicity. A variety of proteomics approaches may be used to address these goals. Two-dimensional gel electrophoresis (2D-PAGE) is the cornerstone of many discovery-based proteomics studies. Technologies such as laser capture microdissection (LCM) and highly sensitive MS methods are currently being used together to identify greater numbers of lower abundance proteins that are differentially expressed between defined cell populations. Newer technologies such as reverse phase protein arrays will enable the identification and profiling of target pathways in small biopsy specimens. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) analysis enables the high throughput characterization of lysates from very few tumor cells or body fluids and may be best suited for diagnosis and monitoring of disease. Such technologies are expected to supplement our arsenal of mRNA-based assays, and we believe that in the future, entire cellular networks and not just a single deregulated protein will be the target of therapeutics and that we will soon be able to monitor the status of these pathways in diseased cells before, during and after therapy.
Wulfkuhle
Julia D
JD
FDA/NCI Clinical Proteomics Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. wulfkuhle@cher.fda.gov
Paweletz
Cloud P
CP
Steeg
Patricia S
PS
Petricoin
Emanuel F
EF
Liotta
Lance
L
D014408:Biomarkers, Tumor / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D006801:Humans; D007834:Lasers; D042282:Microdissection; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*; D010449:Peptide Mapping; D010766:Phosphorylation; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome; D012333:RNA, Messenger