Clinical proteomics: translating benchside promise into bedside reality

Key Points Early detection of cancer should increase the likelihood that treatments achieve a true cure. However, several cancers, such as ovarian cancer, lack a specific symptom and a specific biomarker, and accurate and reliable diagnostic non-invasive modalities. The microenvironment of the tumor–host interaction is a potential source for biomarkers that could be shed into the serum proteome. However, looking for single proteins with expression levels in serum that are altered significantly as a result of the disease process is laborious and time consuming. Analysis of serum proteomic patterns comprising many individual proteins, each of which independently were not able to differentiate diseased from healthy individuals, has recently been shown to provide a diagnostic end point for cancer detection. Analysing the proteins that change in actual diseased human tissue offers new opportunities for the identification of therapeutic targets. Laser-capture microdissection (LCM) is a technology for procuring pure cell populations from a stained tissue section under direct microscopic visualization, and has been applied to discover new protein targets that are either a cause, or consequence, of the disease process in the actual tissue. A new type of protein array — the reverse-phase protein array — is particularly suited to analysing protein signalling pathways using small numbers of human tissue cells microdissected from biopsy specimens procured during clinical trials. In summary, clinical proteomics could have significant potential in the following crucial elements of patient care and management: early detection of the disease using proteomic patterns of body fluid samples; diagnosis based on proteomic signatures as a complement to histopathology; individualized selection of therapeutic combinations that best target the patient's entire disease-specific protein network; real-time assessment of therapeutic efficacy and toxicity; rational redirection of therapy based on changes in the diseased protein network that are associated with drug resistance. Combinatorial therapy, in which the signalling pathway itself is viewed as the target rather than any single 'node' in the pathway, might offer new opportunities at increasing efficacy while decreasing toxicity. The ultimate goal of proteomics is to characterize the information flow through protein networks. This information can be a cause, or a consequence, of disease processes. Clinical proteomics is an exciting