Noninvasive molecular detection of cancer -- the bench and the bedside

The more profound understanding of the genetics and molecular pathways driving human tumorigenesis is paralleled by an ongoing interest to translate this knowledge into development of cancer biomarkers, termed molecular tumor markers. The molecular changes observed in tumors frequently constitute early events which are detectable as signatures of malignancy in body fluids and their occurrence may precede clinical cancer diagnosis. Thus, beyond applicability on tissue samples, molecular markers for tumor signatures should allow noninvasive or minimally invasive diagnosis in blood and/or other body fluid samples. However, to qualify as a clinically useful molecular tumor marker for initial diagnosis and detection of recurrent disease, a molecular tumor marker must have better test characteristics (sensitivity, specifity) than currently applied tumor markers. A molecular tumor marker should also be suitable for screening purposes by defining the subset of individuals for which definite cancer diagnosis by more invasive and/or expensive additional investigations is indicated. In addition, there is a demand for molecular tumor markers to be used as reliable surrogate endpoints in cancer prevention trials. Recommendation for the use of individual molecular tumor markers within evidence-based medicine criteria should ideally be derived from their overall efficacy to reduce tumor-specific mortality. This review focuses on DNA based, RNA based and proteomics based molecular methods of noninvasive cancer detection in bodily fluids and assess the value of these methods for the current and future clinical management of cancer patients.