Abstract
After the human genome was sequenced, pharmaceutical and biotechnology
companies hoped that their enormous investment in drug discovery and
development programs--$51.3 billion in 2005--would yield higher R&D
productivity. However, the industry's target-based research approach has
failed to generate many drugs that work via novel mechanisms of action, and
drugs that fail late in clinical trials significantly drive up the overall
cost of drug development. Companies are now reevaluating their drug discovery
research strategies, implementing or considering a shift to a pathway-based
approach in the hopes of unlocking the promise of genomics-based drug
discovery. By studying the routes by which drugs act on a system (i.e., a
signaling pathway or network) rather than simply scrutinizing a specific
target, companies hope to better understand how a disease progresses, which
they hope will in turn lead to better-designed and more effective therapeutic
strategies. In this report, we discuss recent progress in pathway-based drug
discovery. We review studies aimed at expanding researchers' knowledge of key
pathways and those that use whole-pathway screening methods. We also highlight
the application of pathway-based methods to drug discovery and translational
medicine and discuss the impact of pathway-based strategies on pharmaceutical
R&D
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