Chapter 18. Antineoplastic Agents

Abstract

Publisher Summary A common strategy of anti-neoplastic drug discovery in the past several years has been to discover the way by which an effective anti-cancer agent works and use this knowledge in a mechanism-based drug discovery program to find new structures that work by a similar mechanism but have greater activity and/or fewer side-effects. The majority of this chapter focuses on promising new agents that have entered clinical trial in the past few years, preclinical compounds with a degree of efficacy in animal models that would appear to warrant development to clinical trial, and compounds that demonstrate unique mechanisms or unusual activities in preclinical studies. The exceptional preclinical profiles and apparent clinical efficacy of compounds related to camptothecin has spawned a search for other classes of compounds that produce DNA damage mediated by topoisomerase I. Several clinically useful anti-neoplastic agents inhibit DNA topo II. Among the inhibitors of this important enzyme, three compound classes have shown promise in ongoing clinical trials: anthrapyrazoles, ellipticines, and amonafide. There are a number of agents with either novel or unknown mechanisms of action that are currently being evaluated as anti-cancer agents. Much of the focus in anti-cancer drug discovery has been directed away from agents that kill cells by producing DNA damage and toward modulators of signal transduction pathways that have become unregulated or otherwise aberrant in malignant transformation. Anti-neoplastic agents with completely novel mechanisms of action are the subject of intensive preclinical study and may begin to impact on cancer treatment toward the end of the decade. The anti-cancer agents currently showing promise in clinical trials operate by mechanisms similar to those of the established drugs.