Cancer diagnostics based on plasma protein biomarkers: hard times but great expectations

Cancer diagnostics based on the detection of protein biomarkers in blood has promising potential for early detection and continuous monitoring of disease. However, the currently available protein biomarkers and assay formats largely fail to live up to expectations, mainly due to insufficient diagnostic specificity. Here, we discuss what kinds of plasma proteins might prove useful as biomarkers of malignant processes in specific organs. We consider the need to search for biomarkers deep down in the lowest reaches of the proteome, below current detection levels. In this regard, we comment on the poor molecular detection sensitivity of current protein assays compared to nucleic acid detection reactions, and we discuss requirements for achieving detection of vanishingly small amounts of proteins, to ensure detection of early stages of malignant growth through liquid biopsy.