Abstract
The shift from traditional to genomics-and proteomics-based drug discovery has fundamentally
changed the way researchers view the subject of targets. After decades of focusing on a few hundred
relatively well-characterized therapeutic targets, drug developers are now finding that the genomics
revolution has presented them with the opposite dilemma: thousands of prospective targets about
which little is known. Powering Discovery through Target Evaluation: Moving beyond the Validation
Paradigm comprehensively evaluates current efforts to solve the target validation problem.
With steadily growing drug development costs, depleted pipelines, and few blockbusters on the
horizon, the ability to quickly identify the most biologically promising of these targets will be
the single-largest differentiator between the winners and losers within the research-based
pharmaceutical industry over the next decade. Target validation thus becomes the central issue in
the success or failure of pharmaceutical R&D. Researchers must find the means to choose the best
drug targets early in the process to reduce costly attrition rates and allow for more efficient drug
discovery and development.
Powering Discovery through Target Evaluation: Moving beyond the Validation Paradigm offers unique
and insightful analysis of current efforts to sift through the post-genomic data deluge, prioritize
targets, and optimize resources to develop the most promising leads. This report:
- Reviews the key issues with the current target validation paradigm.
- Evaluates the tools and business strategies of select companies competing in this arena.
- Analyzes efforts to use proteomic techniques for target validation.
- Addresses applications of RNAi technology to target validation and pathway mapping.
- Examines the issue of multiple molecular "causes" of disease by developing therapies
(including single drugs and combination therapies) that address more than one molecular target.
- Discusses whole pathway approaches to drug discovery--a crucial step toward understanding the
function of poorly characterized targets. Pathway analysis may also be important in patient
stratification.
- Evaluates the current status of translational medicine as a strategy for improving the
productivity of drug development.
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