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Introduction
The public, and the biomedical community, have an insatiable appetite for new anticancer drugs. Word-wide, over 800 new anticancer agents are currently in Phase I clinical
trials. The public’s needs are often driven by personal experience, and their expectations are frequently heightened by media coverage (and hype) of what new drugs may promise.
We, as scientists and clinicians, the cancer research community, are not only quite rightly informed by patient need. We are also increasingly optimistic about the dramatic increases
in our understanding of the underlying biology, biochemistry and genetics of human cancers over the past 20 years. We hope that all this can be translated into altogether more
effective and less toxic treatments than could inherently be achieved in the past with classic non-selective anticancer agents.
This book has its origins in my experiences at the Institute of Cancer Research UK, when I was privileged to come into contact with a number of visionary clinicians and scientists,
especially Tim McElwain, Tom Connors and Ken Harrap, who were instrumental in the development of cancer therapeutics as a discipline. In this spirit I hope that this book plays
a role in fostering its unique interplay of fundamental and translational aspects of cancer drug discovery. Its central aim is to provide detailed accounts of the twenty-fi rst century
cancer drug discovery process, from target identifi cation and validation, through lead discovery and optimization to pharmacological evaluation and eventual clinical trial, so that
the reader emerges with a broad overall view and, most importantly, understanding of the key issues and complexities involved. The book is divided into fi ve parts: Basic Principles,
Methodology, Drugs in the Clinic, New Agent, and The Reality of Cancer Drugs in the Clinic. The fundamentals of cancer biology are not described since the reader is well served
by a number of excellent books, with that by RA Weinberg (The Biology of Cancer, Garland Press, 2006), being especially recommended. Case histories of particular drugs feature in a
number of chapters throughout of book, and some also conclude with questions that can be used in a classroom setting.
Chapters in the fi rst section introduce the process of drug discovery, and cover such topics as druggable targets, the scope and limitations of animal models, and the issues surrounding
clinical trial design and regulatory approval. Hand-in-hand with the advances in our knowledge of the molecular basis of cancer have been advances in key enabling areas of science and technology, notably chemistry, structure-based design and pharmacokinetics. These are described in the second section. Chemistry concepts in particular, also pervade many of the subsequent chapters. Parts III and IV describe a number of the established and emerging new cancer targets respectively, and the drugs that have been developed against them. Drug discovery in general, and cancer therapeutics in particular, is fraught with diffi culties. We can be confi dent of predicting that less than one percent of those 800 agents in Phase I will eventually make it to registration and clinical utility. So how can we improve on this very high failure rate? The chapters in the fi nal part focus on the challenges of issues such as drug resistance, and importantly analyze the basis of some existing drug failures.
I am very grateful to all the contributors, not only for their hard work, but also for their cooperation in meeting challenging deadlines. Production of any book is a complex operation,
involving many people. This book is no exception. The staff of Elsevier have been enormously skillful and professional, especially Kirsten Funk, who has been instrumental in guiding this project through its many ups and downs. My assistant in London, Irene Dougherty, has played a key role in maintaining regular contact with the contributors. Last, but not least, many thanks to my wife Andrea for her support and patience.
Stephen Neidle
London, August 2007
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发表于 2012-11-1 10:55:34
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发表于 2012-11-1 11:04:36
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