Innovative Proteomics for the Discovery of Systemically Accessible Cancer Biomarkers Suitable for Imaging and Targeted Therapies

The discovery of biomarkers that are readily accessible through the circulating blood and are selectively over-expressed in pathological tissues has become a major research objective, particularly in the field of oncology. Indisputably, this group of molecules has a high potential to serve as an innovative tool for effective imaging and targeted cancer therapy approaches. In this attractive therapeutic concept, specific cancer proteins are reached by intravenously administered ligands that are coupled to cytotoxic drugs. Such compounds are able to induce cancer destruction while sparing normal tissues. Owing to the performance of mass spectrometry technology, current high-throughput proteomic analysis allows for the identification of a high number of proteins that are differentially expressed in the cancerous tissues. However, such approaches provide no information regarding the effective accessibility of the >biomarkers and, therefore, the possibility for these discovered proteins to be targeted. To bypass this major limitation, which clearly slows the discovery of such biomarkers, innovative methodological strategies have been developed to enrich the clinical specimens before the mass spectrometry analysis. The focus is laid on the group of proteins that are necessarily located either at the exterior face of the plasma membrane or in the extracellular matrix. The present review addresses the current technologies meant for the discovery and analysis of accessible antigens from clinically relevant samples. (Am J Pathol 2011, 178:12-18. DOI: 10.1016/j.ajpath.2010.08.004)