Many fronts in war on mutants

The Biology of Cancer. First Edition - The Molecular Biology of Cancer. First Edition - Cancer Biology. Third Edition

February 23, 2007

As medical students in the 1950s, we were taught that an understanding of the biological basis for cancer presented an intractable problem with little hope of a solution in our lifetimes. Indeed, quoting a distinguished London surgeon, our teachers suggested that it would not be solved by men in white coats working in a laboratory but, rather, by somebody leaning over a fence watching workmen dig a hole in the road.

Since the same teachers told us that duodenal ulcers were holes in the bowel through which men escaped from difficult wives, perhaps it is not surprising that we were sceptical of the "road-to-Damascus" solution to the cancer problem. And we were right: the remarkable insights into the nature of cancer of today are the fruits of more than 50 years of intensive laboratory research, in the large made possible by the advent of cell and molecular biology.

The first hints of success came from the observation that many tumour viruses carry one or more genes, viral oncogenes, that are responsible for their ability to produce cancer. In 1989, Michael Bishop and Harold Varmus made the remarkable discovery that all living organisms, including human beings, have genes that are very similar to viral oncogenes. These homologues were called cellular oncogenes, an unfortunate term as it turns out because they are part of our cells' normal genetic machinery responsible for the control of their proliferation differentiation and development. By the amalgamation of knowledge obtained from classical epidemiology, cytogenetics, molecular and cell biology and tumour virology, it is now clear that most cancers result from the acquisition of mutations in cellular oncogenes; rarer and often familial cancers may be caused by mutations in a related group of genes called tumour suppressors. The action of many of these genes is now fully worked out at the molecular level, and this knowledge is having practical application in the clinic for the diagnosis and targeted treatment of many forms of cancer.

Although many questions remain, there is no doubt that the elucidation of the molecular basis for the malignant transformation of cells has been the most successful medical application of molecular and cell biology so far.

For not only has it helped us to understand the biology of cancer, but it has also provided important lessons for many other fields of biology and medicine, in particular immunology and developmental biology. This rapidly moving field is becoming an essential part of undergraduate and postgraduate teaching in many courses in biology and medicine. Hence these three books are a welcome addition to the limited number of student texts in this field.

Writing textbooks on this topic presents a number of formidable problems for their authors. Cancer now spans many fields of biology, ranging from classical genetics, epidemiology, public health and whole-organ pathology, through molecular and cell biology, to diagnostics, preventative medicine, therapy and palliative care. The courses that students will have to be prepared for vary widely in their level of integration of these topics and differ depending on whether they focus on the basic biological sciences or clinical medicine. No student textbook can cover all these issues; the question is how to present the molecular and cellular aspects of cancer within this particularly broad biological framework. Each of these books has tackled this problem in a slightly different way, the emphasis reflecting the different interests and objectives of the authors.

The Biology of Cancer , written by the distinguished American cancer biologist Robert Weinberg, is by far the most extensive of these new works and, as the product of a single author, is a remarkable achievement.

Weinberg takes a historical approach, describing the field step by step as major discoveries were made. Starting with a description of the basics of Mendelian and molecular genetics and the general nature of cancer, he continues with the discovery of tumour viruses, cellular oncogenes and tumour suppressor genes, with extensive chapters on the molecular pathology of their different classes and the mechanisms of metastasis and finishes with an outstanding section on the more rational treatment of cancer. Each chapter ends with a forward-looking summary "Synopsis and prospects", a list of key concepts and a set of questions. Scattered about the text are numerous commentaries that detour slightly from the main thrust of the discussion. The book includes a valuable CD-Rom package, mini-lectures on certain topics that will be available on the CD in a format that can be transferred to an MP3 player, and items and future media updates that will be available to students at <a target="_blank" href="http://www.garlandscience.com.">www.garlandscience.com.</a> The book is beautifully illustrated in full colour and well supplied with key review articles. It is extremely well written in language that should be accessible to the non-expert.

As is inevitable in an extensive coverage of a complex field by a single author, there are a few problems with historical presentation, such as the omission of David Lane and Lionel Crawford's discovery of the p53 protein in parallel with Arnold Levine, and a few errors, Table 12.1 and Figures 12.23 and 12.33 for example. But these can be easily corrected in future editions, and there are sure to be many. Overall, this is a remarkable achievement that is by far the most comprehensible coverage of this field available.

The second book in this trio, The Molecular Biology of Cancer , is a multi-author work edited by Stella Pelengaris and Michael Khan. While covering much of the same ground as Weinberg, although in much less detail, it takes a rather broader view of the cancer field, in particular in terms of diagnostics and clinical care, including palliation and terminal symptom control. There are particularly good accounts of epigenetic manifestations and cell-cell interactions in the generation of cancer. Each chapter carries a valuable table of key points, remaining questions and conclusions and future directions. It is clearly illustrated in black and white and, for the most part, very well written. The accompanying website (www.blackwellpublishing. com/pelengaris) contains a more comprehensive reference list and will be updated regularly.

The third edition of Cancer Biology by Roger King and Mike Robins is based on a course given to final-year students in the School of Biological Sciences at Surrey University. It appears to have been revised extensively for this new edition, which offers a clear summary of the molecular basis of cancer together with up-to-date sections on the principles of cancer treatment and approaches to its prevention. It, too, is well written in a language that will be accessible to non-experts, and it is attractively illustrated in two-tone. Overall, it seems likely to continue to be as popular with students of medicine or biology as its predecessors.

These are three excellent books. Weinberg's tour de force will undoubtedly become a standard reference, not just for science or medical students but for graduate research workers and throughout the field of oncology research. The other two can also be strongly recommended to students of biology or medicine; overstretched medical students may find the shorter and broader treatment of King and Robins of particular value.

David Weatherall is regius professor of medicine emeritus, Oxford University, and chancellor, Keele University.

The Biology of Cancer. First Edition

Author - Robert A. Weinberg
Publisher - Garland Science
Pages - 864
Price - £41.99
ISBN - 0 8153 4076 1

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