Cancer biomarkers: surviving the journey from bench to bedside.

In summary, the abundance of reported candidate-biomarker proteins in the scientific literature compared to the lack of those reaching clinical use indicates that the aforementioned pipeline bottleneck falls in either the verification or validation phases. To stress this point, Polanski and Anderson compiled a list of 1,261 proteins that have been cited in the literature as being differentially expressed in human cancers.¹ Of the 1,261 proteins, 22% are reported to be present in the blood and should be detectable given a sensitive enough assay. Interestingly, only 5% of these candidates have been thoroughly investigated as biomarkers (greater than 500 citations),¹ with 41 (~3%) actually being used in some clinical capacity. The reason behind so few biomarkers reaching the clinic can largely be explained by the inability of current technologies to consistently and quantitatively verify the presence of the candidates in patient samples and the failure, thus far, to identify biomarkers with high specificity for a particular disease.⁹ As noted above, none of the nine FDA-approved cancer biomarkers demonstrate the specificity required for diagnosis when used alone. Thus, the development of panels of proteins, such as the FDA-approved OVA1 test,⁵⁷ may be crucial to achieve the specificity required for early cancer diagnosis, and is interesting to speculate that members of such panels are likely to have already been identified but not yet implemented.⁵⁸