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6 January 2014

978 0 81534 220 5
Garland Science
GBP 55

The Biology of Cancer (2nd edn)

Robert A. Weinberg

For this review, I performed an advanced PubMed search on Weinberg RA. It returned 375 papers, of which 44 were published in Cell, 32 in Nature and 14 in Science, the vast majority citing Professor Weinberg as corresponding author. As empirical evidence goes, there can be no doubt the massive contribution made by one individual and his group to cancer research down the years. On Professor Weinberg’s website at the Whitehead Institute of Biomedical Research at MIT, there are group photographs from the 1970s with the current one portraying a distinct tongue-in-cheek homage to the principal investigator. This book, these images and this author present an overall impression of a likeable brilliant scientist with a phenomenal research pedigree and a consummate ability to understand and dissect the enigma that is cancer. That this scientist is responsible for this book will make The Biology of Cancer stand out as a seminal text providing cancer researchers with a contemporary reference second to none.

It is impossible to cite any one area of cancer research as being more important than another. But, for me, one area does stand out in this book and that is p53. Cited as the master guardian and executioner of the genome, this 53 kDa nuclear protein rapidly turns over and directs cells towards quiescence or apoptosis in times of proliferation malfunction or physiological stress. However, it is also central to many cancer pathologies thanks to the frequency and number of mutated p53 alleles present in human cancer cells. With a helpful DVD-ROM, one such mutation at Arg248 which hinders binding of p53 to DNA is graphically delineated. Functional loss of p53 has distinct downstream consequences: altered DNA binding of p53 target genes (more than 120 so far identified) and aberrant post-translational modification of p53 via phosphorylation, ubiquitylation, methylation and SUMOylation to name but a few. The author speculates why the human genome invests so much in p53, as, when its functional output has been abrogated for whatever reason, there is an apoptotic inevitability to the fate of that cell. Needless to say, p53 is not the only focus of this book; researchers with favourite proteins and molecules from Arf1 to ZEB2 are well catered for.

The book also explores paradigm model signalling cascades. One such example, in the Ras/Raf pathway, mitogen-activated protein kinases (MAPKs) transduce extracellular signals converting them into downstream intracellular functions (transcription, protein synthesis etc.). Diversity at the protein level (e.g. MAPKs, MAPKKs and MAPKKKs) and DNA level, e.g. domains such as PDZ, DED, BRCT, allow for multitudinous protein–protein interactions and functions. When signalling becomes ‘exaggerated’, the consequences to these synchronized and temporal pathways can become constitutive and fatal to the cell.

In terms of presentation, all 900 or so pages are well laid out and easy to read. The writing is so accessible it belies the complexity of the subject; the author has a gift for conveying a clear unambiguous message. Liberally sprinkled throughout are figures and diagrams (accompanied by some very detailed figure legends) taken from current primary research papers, so, importantly, much of the information is up to date. Also included are ‘Sidebars’ which are clinical, medical and research abstracts detouring from the main text into subjects which may prove interesting to some readers. Examples of these include “consequences of gene therapy”, “tumour growth post breast cancer surgery” and “alternative function of cyclins”. As mentioned, an accompanying DVD-ROM depicts some molecules and mechanisms found in cancer progression. There is also a poster included to brighten up that dull laboratory wall!

Cancer aetiology and research are compounded by its extraordinary heterogeneity, so books such as this help scientists gain global insights into mechanistic and hypothetical commonalities that more than likely exist at the molecular level. Costing approximately £50, this book is incredible value for money and I would recommend it to all researchers and laboratories conducting cancer research.

John P. Phelan (Waterford Institute of Technology, Ireland)

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