Hypoxia-Induced Factor-1 as a Target for Anticancer Therapy

One of the most powerful recent advances in drug discovery has been the development of high-throughput screens that rapidly identify small molecules having specific biochemical, biological, and ultimately therapeutic effects. A candidate high-throughput screening target is ultimately validated only by the successful development of a pharmaceutical agent. For a putative target, there are three major points that need to be addressed to evaluate its anticancer potential. First, is the target in question important for the proliferation, survival, or metastasis of tumor cells? Second, is the target tractable for lead identification by high-throughput screening? Third, are facile methods available for determining if a candidate lead molecule effectively inhibits target function in vitro and in vivo? The purpose of this chapter is to address these issues with regard to the transcription factor HIF-1 (hypoxia-induced factor-1), and assess its suitability as a target for anticancer drug development.