パスウェイアプローチは標的創薬の問題を克服できるか？

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

Table of Contents

Introduction

The Success of Traditional Pathway Studies

The Need for New Pathway-Based Knowledge and Approaches

Elucidating Signaling Pathways and Identifying Drug Targets

• Technologies
  • Yeast Two-Hybrid Assay
  • Tandem Affinity Purification
  • RNAi
• Strategies
  • Cellzome's Study of the TNF-α/NF-κB Signal Transduction Pathway
  • Hybrigenics' Study of Signal Transduction Pathways in Drosophila

Pathway-Based Drug Screening Technologies and Strategies

• BioImage's Redistribution Technology
• Bionaut's Sentinel Line Technology
• BioSeek's BioMAP Systems
• Avalon Pharmaceuticals' Pathology-Based Screens

Novartis's Pathway-Based Drug Discovery Strategy

Corporate Highlights

• Bionaut Pharmaceuticals
• BioSeek
• Cellzome
• BioImage
• Hybrigenics

Outlook for Pathway-Based Drug Discovery