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12 August 2013

978 0 82475 494 5
CRC Press
GBP 185.00

Metal Ions in Biological Systems Volume 42: Metal Complexes in Tumor Diagnosis and as Anticancer Agents

A. Sigel and H. Siegel (eds)

Although not being the stuff of book reviews, the first thing that strikes you about this book is how much it weighs. If ever there was a relationship between academic rigour and weight, this book would exemplify that relationship in a most spectacular fashion (incidentally I did not weigh it – it would have been too peculiar to explain to my colleagues!). What cannot be denied is the volume of knowledge contained in this book on everything to do with metals, e.g. platinum, palladium, sodium and gold etc., and their roles in biological tissue and disease treatment. Introducing and exploring the novel ‘bioinorganic chemistry’ concept, the pages are filled with examples of how biological metal-ion-containing compounds are used in medicine to combat a wide variety of diseases, namely cancer. As an academic tome, it is not given over to being read from cover to cover (nearly 500 pages); rather the index was searched for terms relevant to my own work and interests which were mainly medical and clinical perspectives.

The serendipitous discovery of cisplatin in 1965 has made massive inroads into cancer treatments which today rakes in over US$1 billion dollars per annum. Successful in treating many cancers, the anticancer drug (on its own or in combination therapy) has an over 90% cure rate with testicular cancer. Similarly, cisplatin in combination with chemotherapy can have dramatic effects on non- small-cell and small-cell lung cancers. Previous evidence of cellular uptake has pointed to the mechanism of passive diffusion; however, in vitro studies using human cell lines and Saccharomyces cerevisiae deletion mutants have uncovered more in-depth mechanistic insights revealing copper transport to be critical for approximately 50% of the uptake. Inside the cell, cisplatin can bind to RNA, proteins or sulfur-containing biomolecules, but the prevailing opinion is that cisplatin interacts primarily with G-rich DNA sequences. However, there is controversy which is explored in detail in the book, but is beyond the scope of this review.

Unsurprisingly, the index reference for metal ions implicated in cancer treatment is large and extensive. Prominent is photodynamic therapy which is rapidly becoming a mode of treatment in many clinical settings. Exploiting the accumulation of porphyrins in cancer cells/fast-growing tissues, porphyrin photosensitizers are administrated via intravenous injections to localize to cancerous regions. Visible red light applied to the area activates the sensitizer producing singlet oxygen, the cytotoxic agent. The search is now on for other porphyrin derivatives with greater potency. One such example is the texaphryins which are embedded deep in human tissues, but, with the application of near infrared light (700 nm), tumours can be targeted successfully as is the case with cancer phototherapy, photoangioplasty (removal of atheromatous plaques) and age-related macular degeneration.

The one striking theme that dominates this book is that of cellular toxicity. The administration of intravenous metal-ion-based medicines is, in principle, highly beneficial from a clinical perspective; however, the major caveat can be significant toxicity to adjacent tissue. Dotted throughout are clinical and medical notes listing the chronic and acute side effects of these drugs, ranging from neurotoxicity, nephrotoxicity, ototoxicity and myelotoxicity. Although being a panacea in many clinical trials, the use of metal ion therapy has to be weighed up in terms of clinical benefit versus extraneous patient health and wellbeing.

Metal Complexes in Tumor Diagnosis and as Anticancer Agents is volume 42 in a series of compendia that has brought to prominence the role of metal ions in many different biological processes. Printed in 2004, aspects of clinical and medical implications may have changed for example outcomes of clinical trials and likewise the controversy over what cisplatin actually binds to in the cell; nonetheless, the book lays down many basic principles of the role of metal ions in biological processes. Retailing at £185, the book is aimed at established scientists, but is accessible to clinicians and medical personnel involved in the treatment of disorders and diseases using metal-based compounds.

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

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