Cancer cell-based genomic and small molecule screens.
This chapter focuses on the promising post-genomic technologies being used for discovery of new, safer, and better cancer drugs and drug targets. Since cancer is largely a disease of the cell, usually involving unrestricted cell proliferation as a result of heritable genetic changes such as mutation, this chapter will focus on cell-centric technologies and their utility in addressing major questions in cancer biology. Recent advances in cell-based technology, including phenotypic assays, image-based readouts, primary tumor cell growth and maintenance in vitro, gene and small molecule delivery tools, and automated systems for cell manipulation, provide a novel means to understand the etiology and mechanisms of cancer as never before. In addition to the abundant tool sophistication, many aspects of cancer can be emulated and monitored in cell systems, which makes them ideal vehicles for exploitation to discover new targets and drugs. This chapter will first handle nomenclature and provide a context for a "good drug target" within the framework of the human genome, then overview functional genomic gene-based library screening approaches with specific applications to cancer target discovery. Second, small molecule screening applications will be handled, with an emphasis on the new paradigm of massively parallel screening and resultant multidimensional dataset analysis approaches to identify drug candidates, assign mechanism of action, and address problems in deriving selective and safe chemical entities.
Caldwell
Jeremy S
JS
Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA.
D000818:Animals; D015195:Drug Design; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D023281:Genomics / Q000379:methods*; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000379:methods / Q000639:trends*; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering
D034741:RNA, Small Interfering