Approaches to New Drug Discovery

Abstract

For this survey, current approaches to the discovery of new anticancer drugs are discussed in three categories: tumor-directed delivery vehicles, screens for specific protein modulators, and mechanism-blind assays. These approaches are intertwined in several respects (Fig. 12–1). New methods for identifying tumor markers provide novel delivery “addresses” as well as novel targets for drug inhibition or activation. Conversely, proteins identified by genetic epidemiology or cell biology studies as potential intervention points may also provide new addresses. In addition, random screening of novel compounds in cell-based assays, especially natural products, continues to uncover new drug targets. Moreover, cell-based cytotoxicity screening has reached a level of sophistication that allows compounds to be evaluated for novelty in their spectrum of activity before committing to the full expense of clinical development. Closing the loop, gene-transfer technology has provided cell-based screening with new power as a target validation tool, conveniently extendable to animal models via tumor-directed delivery approaches. An important conclusion from this survey is that the logic of current research is increasing the desirability of tailoring treatment protocols to patients stratified by multiple criteria.