Anticancer drug development Academic Press
Due to the tremendous increase in our understanding of the cancer process and cause, development of drugs to selectively interfere with and inhibit tumour growth has now entered a new and exciting era of the target orientated approach. Drugs are now being developed against specific proteins involved in cancer cell growth that have been uncovered over the last 10 years or so. These differences cover all areas of cancer biology, from cell signalling pathways to tumour hypoxia and from angiogenesis to cell death pathways. It therefore follows that to develop drugs that interfere with these complex pathways, a comprehensive knowledge of the cancer process is needed by today's cancer researcher. This book gives a very comprehensive overview of the whole of the anticancer drug development process today, from chemical synthesis to the clinic.
The book begins with a brief chapter on the history of chemotherapy describing the problems of today's anticancer drugs, the lack of specificity or low therapeutic index. Individual sections on specific areas follow, where the emphasis is on uncovering new targets for therapeutic interference. These include the cell cycle, signal transduction pathways and apoptosis. Not only are these detailed and up-to-date reviews of the topic, but highlight areas of possible therapeutic intervention throughout the text, including compounds that are already known to act on these areas, very useful for those not familiar with the field. Each chapter concludes with strategies for future drug development.
Attempts at inhibiting the cancer metastatic process have been high profile recently with the MMP inhibitors, Batimastat and Marimastat, entering the clinic. Cancer metastasis is a complex process, and this chapter not only gives an overview of the subject but also describes in some detail the thinking behind the design of existing and future MMP inhibitors.
Drug resistance pathways have long been an area of interest for therapeutic intervention and these are brought up-to-date with our current understanding of P-glycoprotein, NF-κB and the potential role of tumour physiology in drug resistance. Anti-angiogenic drugs and antivascular agents are not quite the same but have been grouped to cover all aspects of tumour vasculature as a target. Here we see slight overlap with other chapters, and indeed the editors do comment on the overlap between chapters as each chapter is written by independent authors. This overlap is inevitable (but minimal), as tumour vasculature and angiogenesis is bound to overlap with MMP expression and inhibition which is bound to overlap with cell signalling, and so on. The GDEPT concept is dependent on the activation of prodrugs at the tumour site. Several useful enzyme-prodrugs systems are covered here as well as the latest antigenic targets available for ADEPT. These are two concepts that have shown promise preclinically but are still under development in the clinic.
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