The Handbook of Biomarkers
Of the thousands of biomarkers that are currently being discovered, relatively few are being validated for further applications, and the potential of a biomarker can be quite difficult to evaluate. To aid in this imperative research, Dr. Kewal K. Jain’s H
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Biomarkers for Drug Discovery and Development
Introduction Among the current applications of biomarkers those for drug discovery and development are one of the most important. Biomarkers are used in new approaches to remedy the shortage of new drugs and to the current lengthy and expensive process of drug development. Biomarkers can be used to predict and confirm target binding, to determine mechanism of action of a drug, pharmacokinetics, toxicity, and to monitor disease status, stratify patients, and determine treatment efficacy in clinical trials. The parallel role of biomarkers in the drug discovery process is shown in Fig. 4.1. For biomarkers to assume their rightful role, greater understanding of the mechanism of disease progression and therapeutic intervention is required. Biomarkers should be considered while the therapeutic target is still being identified and the concept is being formulated. Exploratory biomarkers lay the groundwork for probable or known valid biomarkers and are useful for hypothesis generation. They fill in the gaps created by uncertainty of disease targets and variability in drug response. Institution of biomarker strategies early in drug development will facilitate the processes for bridging from preclinical to clinical development. These include identifying the biomarkers that will enable compound profiling, the clinical decision tree algorithms, and developing and validating the assays that will measure them. Biomarker-based drug development also integrates pharmacogenetics, pharmacogenomics, pharmacoproteomics, which are relevant to the development of personalized medicine (see Chapter 9). Understanding the molecular basis of disease will limit failure in drug development due to wrong biological hypotheses. Most of the emphasis on biomarkers in drug development is on early identification of potentially successful molecules to predict potential efficacy and safety. However, it is important that biomarkers be chosen, developed, and evaluated in a way that enables them to provide confidence to terminate a molecule when it has no effect on the biomarker. This is clearly a challenge for novel molecules that are the first in their class, but it can be achieved through building a sound theoretical rationale for the biomarker supported by evidence of linkage to the effect of the drug in appropriate animal models.
K.K. Jain, The Handbook of Biomarkers, DOI 10.1007/978-1-60761-685-6_4, C Springer Science+Business Media, LLC 2010
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4 Biomarkers for Drug Discovery and Development Target discovery
Target validation
Discovery of biomarkers
Clinical trials discovery
Preclinical
Probably valid biomarkers
Valid biomarkers
Fig. 4.1 Role of biomarkers in drug discovery and development process
It is worthwhile to develop biomarkers for exploring the pharmacology of new molecules and to develop potential biomarkers of efficacy. A molecule that does not have the intended pharmacological effect is unlikely to have the desired efficacy and its development should be terminated. Discovery
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