Unleashing the Power of Proteomics to Develop Blood-Based Cancer Markers

Abstract

BACKGROUND There is an urgent need for blood-based molecular tests to assist in the detection and diagnosis of cancers at an early stage, when curative interventions are still possible, and to predict and monitor response to treatment and disease recurrence. The rich content of proteins in blood that are impacted by tumor development and host factors provides an ideal opportunity to develop noninvasive diagnostics for cancer. CONTENT Mass spectrometry instrumentation has advanced sufficiently to allow the discovery of protein alterations directly in plasma across no less than 7 orders of magnitude of protein abundance. Moreover, the use of proteomics to harness the immune response in the form of seropositivity to tumor antigens has the potential to complement circulating protein biomarker panels for cancer detection. The depth of analysis currently possible in a discovery setting allows the detection of potential markers at concentrations of less than 1 μg/L. Such low concentrations may exceed the limits of detection of ELISAs and thus require the development of clinical assays with exquisite analytical sensitivity. Clearly the availability for discovery and validation of biospecimens that are highly relevant to the intended clinical application and have been collected, processed, and stored with the use of standard operating procedures is of crucial importance to the successful application of proteomics to the development of blood-based tests for cancer. SUMMARY The realization of the potential of proteomics to yield blood biomarkers will benefit from a collaborative approach and a substantial investment in resources.