Within Sight of a Rational Pipeline for Development of Protein Diagnostics

Given the paucity of new clinical tests emerging from proteomics research on the one hand (1) and the large and increasing levels of NIH funding devoted to biomarker research on the other (2), important questions have been raised about our strategy for translating basic research into clinical diagnostics. At a fundamental level, it has been unclear whether the lack of clinical results from numerous biomarker discovery efforts is due to our having exhausted the low-hanging fruit (or all fruit?) in years past, or to defects in the approaches being used in the search for new markers. It seems unlikely that all useful clinical protein tests have been discovered; therefore, discussion has focused on the defects in the “biomarker pipeline” that should be conveying candidate biomarker proteins toward a clinical application. The ultimate importance of this debate is not academic: Improvements in clinical care and in basic health economics increasingly depend on the development of new tests (including companion diagnostics that allow personalization of therapy) and markers addressing the long-standing list of unmet clinical diagnostic needs in such areas as Alzheimer disease, chronic obstructive pulmonary disease, and cancer.Fortunately, recent publications (3, 4) suggest that progress is being made in implementing biomarker pipeline concepts that work: approaches that link a “discovery” process that uses a small number of particularly favorable samples with one or more “qualification” and/or “verification” steps that focus on testing the resulting candidate biomarkers with independent sets of real clinical samples. The work of Addona et al. (3) serves as a useful benchmark in this context because it is focused on a clinical indication (cardiac damage markers) in which numerous proteins, such as creatine kinase isoenzyme MB, troponins, and B-type natriuretic peptide, have achieved undisputed clinical success. One can thus ask whether such a modern systematic approach …