This work presents a comprehensive contemporary framework for approaching target validation in drug discovery. It begins with a detailed description of new enabling technologies, including aptamers, RNA interference, functional genomics, and proteomics. The next section looks at biologic drug development with in-depth discussion of lessons learned from such well-known cases as Erbitux, Herceptin, and Avastin. Additional targets known as "second generation" drugs, which can be identified when disease pathways are validated by biologics, present new possible small molecule therapeutics and serve as the focus of the final section of the book.

This volume focuses on recent developments in our understanding of selected adhesion processes that may offer new approaches to developing therapeutics for a variety ofdiseases. The volume first introduces the molecules involved in key adhesive processes, then describes the biological consequences of several adhe- sive interactions, and closes with a description of the initial therapeutic ap- proaches to antagonizing. adhesion. These papers were originally presented at the SmithKline Beecham Pharmaceuticals Seventh U. S. Research Symposium held in Philadelphia in October of 1992. ofacell to asurface. In its simplestsense, cellularadhesion is the adherence The cells of interest in the context of this volume are bacterial and mammalian, with an emphasis on leukocytes; surfaces can be other cells and tissues (such as bone), matrix proteins, or inanimate objects such as in-dwelling medical devices and catheters. Interaction between adhesion molecules usually results in a spe- cific biological response. Adhesion is a form ofcellularcommunication, and represents the way a cell senses its environment through contact. Like hormones and cytokines, the sol- uble mediators used by cells for communication, adhesion molecules are defined molecular entities that recognize specific receptor structures on the surface to which they adhere. Recent activity has focused on defining the structure of the individual molecules responsible for many types ofcellularadhesion. New adhe- sion proteins are being cloned with the help of specific antibodies and precise functional assays.