Title: Chapter 14. Mechanism-Based Discovery of Anticancer Agents
Abstract: This chapter discusses the use of mechanism-based assays to detect the potential antitumor drugs that interfere with processes relevant to the neoplastic growth and cites examples of compounds identified by such approaches. Agents in preclinical development, discovered by more traditional approaches, are also included, with examples limited to those drugs that demonstrate a degree of preclinical efficacy that would appear to warrant the development to clinical trial. Compounds that have recently entered Phase I clinical trial are also included. Many of these clinical candidates have demonstrated only the modest activity in preclinical tumor models as has been the case for majority of the drugs developed for cancer in the past. Several clinical candidates, however, have shown a spectrum and degree of preclinical efficacy comparable or superior to that of the most effective established antitumor agents. Significant progress has been made in adopting new strategies for the discovery of novel antitumor drugs using mechanism-based assays. Such approaches apply to the targets of the cyiotoxic drugs with established selectivity for tumors as well as to the targets evolving from the study of oncogenes and tumor cell biology. A number of other targets beside those mentioned in the chapter can be exploited. Examples are: recombination pathways and deoxyribonucleic acid (DNA) damage repair, proteases and adhesion molecules involved in invasion and metastasis, endothelial receptors for tumor-derived angiogenesis factors, and protein kinases and phosphatases involved in the control of cell division. Major advances in the understanding of each of these areas are likely to provide further opportunities for drug discovery. It should be noted, however, that the less selective biological screens for new antitumor agents discussed in this chapter continue to identify the novel compounds with interesting activity and selectivity in animal tumor models and, hopefully, in cancer patients. These novel compounds could lead to the identification of new targets relevant to cancer therapy.
Publication Year: 1990
Publication Date: 1990-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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Cited By Count: 10
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