ABSTRACT
Substrate Phage ................................................................................. 210 8.3.4 Subtracted Substrate Phage Library ................................................. 212
8.4 Application of Substrate Phage Display to Cancer Research ....................... 212 8.4.1 Angiogenesis ..................................................................................... 212 8.4.2 Prognostic Markers for Prostate Cancer ........................................... 213 8.4.3 Tumor Invasion and Metastasis ........................................................ 215
8.5 Conclusions ................................................................................................... 219 References .............................................................................................................. 221
8.2 INTRODUCTION
Dysregulation of specic enzymes, such as proteases, protein kinases, and protein phosphatases, has been implicated in various pathological conditions, especially malignancies. Therefore, much effort has been directed towards developing potent inhibitors of specic enzymes for cancer chemoprevention. However, many of these compounds are broad-spectrum inhibitors that show undesirable side effects among these closely related enzymes. Thus, there is still a considerable need for more selective inhibitors and for new and high-quality treatments. A better understanding of substrate specicities of these enzymes may signicantly improve our overall knowledge about these enzymes, and this will facilitate the design and optimization of potent and selective inhibitors. In recent years, high-throughput screening (HTS), where hundreds of thousands of compounds can be tested for activity during a short period, has been increasingly used to discover novel lead candidate molecules. A key step in establishing an HTS format is to identify a highly selective substrate for use in enzyme assays. A basic understanding of substrate preferences allows further clarication of the physiological roles of these enzymes.
