The failure of protein cancer biomarkers to reach the clinic: why, and what can be done to address the problem?

There is a plethora of published cancer biomarkers but the reality is that very few, if any, new circulating cancer biomarkers have entered the clinic in the last 30 years. I here try to explain this apparent oxymoron by classifying circulating cancer biomarkers into three categories: fraudulent reports (rare); true discoveries of biomarkers, that then fail to meet the demands of the clinic; and false discoveries, which represent artifactual biomarkers. I further provide examples of combinations of some known cancer biomarkers that can perform well in niche clinical applications, despite individually being not useful.