ABSTRACT
There are a number of different ways in which new drugs of all types, including anticancer agents, are discovered, and these are explored in this chapter. Before the advent of modern drug discovery technologies such as high-throughput screening and molecular modeling methodologies, anticancer drugs were discovered by nonrational methods such as screening natural product extracts and synthesized organic compounds in cancer cell lines growing either in vitro or in immune-compromised mice (i.e., in vivo). However, historically, drugs have also been discovered through observation of the side effects produced by existing drugs, metabolic studies, or serendipity (i.e., accidental discovery), the best example of which is cisplatin. Modern drug discovery is based on rational approaches which involve the identification of a chemical or biochemical target present (or overexpressed) in a tumor cell but not in healthy cells, which can then be targeted with small molecules or biological agents using an array of drug discovery tools, the most recent of which include genomic-based methodologies, fragment-based approaches, and molecular modeling and high-through-put screening technologies based on artificial intelligence (AI) platforms. However, other useful drug discovery tools are also discussed, including new chemical synthesis and screening technologies, the latest in vivo models and the use of cancer stem cells. The continuing importance of natural products in anticancer drug discovery is also discussed along with the relatively new approach of drug repositioning which involves the identification of new pharmacological activities in existing approved drugs. Finally, some brief comments are provided on the funding of anticancer drug discovery.
