Biomarkers


therapy monitoring, and for prognostication. While single analytes are the simplest application of biomarkers, the desired specificity and selectivi- ty may sometimes require the examination of pan- els of protein and other biomarkers.


Personalised medicine: Biomarkers, by virtue of their potential to differentiate among disease states as well as patient characteristics, are essential for the realisation of personalised medicine and pro- vide a critical link in the bench-to-bedside research effort which translational medicine represents. While oncology is the area of medicine where we have seen most progress to date in the implemen- tation of biomarkers, and thus already a clear move towards personalised medicine, pharmaceu- tical companies are gearing up to extend the con- cept of personalised therapies to many disease areas. Two major challenges – selection of sub- populations of patients likely to show a favourable treatment response, and monitoring therapy effica- cy – can both be addressed with the help of suitable biomarkers. Although biomarkers will play an essential role in realising the envisioned future potential of personalised medicine, their utility requires a substantive effort directed at their clini- cal qualification in appropriately designed clinical trials with well-defined, relevant endpoints and ref- erence cohorts.


DNA/RNA vs protein biomarkers: While plat- forms for high-throughput analysis of DNA vari- ants and mRNA expression profiles have been developed and are in broad use, the results, with regard to the discovery of clinically applicable bio- markers, have so far been somewhat disappoint- ing, owing perhaps to the inability of nucleic-acid based markers to integrate information related to the downstream processing of proteins that may significantly impact the information content of a marker. Also, environmental and lifestyle con- founders are not at all or less likely to be integrat- ed into and reflected by signals obtained from nucleic-acid-based assays.


Stages of biomarker development: The develop- ment of a clinically applicable biomarker is a com- plex process requiring sequential and iterative steps. Often overlooked yet critical to this process are proper preclinical and clinical study design and sample collection. Therefore, these will be given special attention here. Thus, the development stages for biomarkers are: 1) study design, 2) sam- ple collection, 3) biomarker discovery, 4) biomark- er assay development and initial clinical validation, and 5) confirmation and validation of the bio- marker in additional, independent studies. Each stage is dependent on the previous stage, and at each step a close interaction between drug- and


Figure 2


The diagnostic biomarker immunoassay workflow depicts the different phases of diagnostics biomarker development, the interrelationship between the different components during development and the nature of the iterative processes in development to commercial launch


Drug Discovery World Winter 2010/11


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