Extract

The process for discovery and development of biomarkers of solid tumors presents exceptional challenges. The major technical obstacle is the disconnection between the site of their generation (tissue, proximal fluid) and the source of detection (body fluids, predominantly serum and plasma). This single factor limits, in practical terms, the potential pool of biomarkers to those that are secreted, shed, or leaked from the cell surface. On reaching the circulation, a biomarker undergoes “dilution” into a mixture of thousands of proteins that are present at concentrations spanning at least 10 orders of magnitude. Furthermore, the integrity of a circulating biomarker may be compromised by proteolytic degradation or distortion of its posttranslational modifications. Other levels of complexity involve the inherent variability of biological systems (intraindividual and across a population) and ambiguities in defining disease phenotypes. Finally, fundamental and technological difficulties involved in biomarker studies are exacerbated by preanalytical variables associated with sample collection, handling, and storage (1, 2).

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