Biomarkers
Biomarkers make their mark on current research and drug development trends
Biomarkers continue to become increasingly relevant in research and healthcare applications, as evidenced by the global market for products involved in their identification, validation, and use – estimated at $8.3 billion in 2007 and projected to increase to $15 billion in 20101. The accelerating pace of activity in this area is further underlined by a cursory review of the publication space, where the number of relevant scientific articles generated annually has doubled from 20,000 to 40,000 over the past decade (Figure 1).
T
he NIH defines biomarker broadly as “a characteristic objectively measured and evaluated as an indicator of normal biolog- ical processes, pathogenic processes, or pharmaco- logical responses to a therapeutic intervention”2. As such, this term can describe many common assays, physiological measurements, and imaging protocols that speak not only to biochemists, phar- macologists and toxicologists, but also primary healthcare providers. Narrowing the context to drug discovery, biomarkers serve a wide variety of applications from target validation through drug candidate development and clinical trial assess- ment. Both gene expression and protein analyte profiling have been successfully utilised in this regard, however the proteome offers advantages over the transcriptome with respect to the number of relevant variations in protein synthesis, turnover, localisation and post-translational modi- fications that associate to normal biology and dis- ease states. Furthermore, protein analyte targets are often easily accessible through various biologi-
Drug Discovery World Summer 2010
cal fluids including serum, saliva, urine or cere- brospinal fluid.
The notion of a useful biomarker implies sensi- tivity and specificity to the biological state being considered, and must be supported by epidemiolog- ical evidence that links it to a clinical outcome. Validated biomarkers can be used as surrogate end- points to substitute for a clinical end point in drug development, which then allows for early assess- ment of the drug benefit/efficacy. Moreover, select- ed biomarkers can be monitored in preclinical stud- ies using cellular or animal models. For these appli- cations to be useful, however, it is critical that the candidate biomarkers be rigorously qualified through a defined discovery and validation process that includes not only a deep understanding of the physiological relevance of the marker, but also experimental confirmation of the precision, robust- ness and limitations of its use for the intended pur- pose. Collaborations are essential to this effort, and a number of diverse stakeholders have now estab- lished mechanisms to harmonise approaches in
By Stéphane Parent and Dr Gregory Cosentino
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