Pharmacogenomic Testing in Current Clinical Practice

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reality check on the field and a status update on progress toward the implementation of genetically enabled drug prescribing. The book is intended to provide a.
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by a 17-page index, making this book a user-friendly reference. Although the book is replete with figures and tables, these are often not described adequately. Abbreviations are frequently not defined, precluding immediate understanding of

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the concepts conveyed. As such, a list of abbreviations at the beginning of the book would have been helpful. In addition, some of the figures are not of high quality or resolution (e.g., Figures 1.2, 1.5b, and 2.5), diminishing their visual appeal. Despite

these shortcomings, the editors appear to have accomplished their intention of providing biomedical researchers a condensed yet detailed reference on the discipline of translational medicine and applications to early drug development.

This reasonably priced book is particularly recommended for scientists new to the discipline. CONFLICT OF INTEREST The author declared no conflict of interest. © 2011 ASCPT

Pharmacogenomic Testing in Current Clinical Practice: Implementation in the Clinical Laboratory

Edited by Alan H.B. Wu and Kiang-Teck J. Yeo Humana Press, 2011 272 pp., hardcover, $219.00 ISBN: 9781607612827

Reviewed by D Grant1

Together, the scientific disciplines of pharmacogenetics and pharmacogenomics can now claim an almost 60-year history of discovery, clinical

investigation, and molecular mechanistic elucidation of a large and still-expanding body of genetic factors that contribute to variable responses to drugs and other foreign chemicals in human populations. However, the wealth of fundamental pharmacogenetic knowledge that has been generated has led to a disappointingly modest degree of clinical application so far in the practice of pharmacotherapy and in contributing to further optimization of the practice of “personalized medicine.” This failure to meet expectations is largely a consequence of inflated expectations. As a result of the hype that arose from the popular press, the venture-capital sector, and the pharmacogenetics scientific community itself around the turn of the century, both investors and the public were

1Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. Correspondence: D Grant ([email protected])

doi:10.1038/clpt.2011.170 358

being promised that drug prescribing was mere years away from patient trips to the pharmacist, gene chip in hand, to receive the perfect drug every time. In the vein of several recent critical reviews on the topic, this new monograph from editors Wu and Yeo aims to provide a much-needed reality check on the field and a status update on progress toward the implementation of genetically enabled drug prescribing. The book is intended to provide a comprehensive reference regarding current and future opportunities, challenges, and practical obstacles to pharmacogenetic testing and interpretation for a target audience that includes basic and clinical researchers and clinical testing laboratory personnel. With some exceptions, it succeeds in accomplishing this aim. The book is divided into five sections. The first is a four-chapter overview

of basic concepts, and the subsequent four sections each contain two to four chapters on pharmacogenetic testing for cancer chemotherapeutic drugs, cardiovascular drugs, drugs causing delayed hypersensitivity, and miscellaneous other drugs, respectively. Certain chapters in the first section on basic concepts are uneven in terms of the degree of detail provided, or they wander from their expected central focus. For instance, Chapter 2 fluctuates in tone between a superficial overview of technical approaches to genotype analysis and a technical laboratory manual—in the latter case, including a specification of the spectrometric absorbance value of DNA at 260 nm in the description of DNA quantitation and purity determination. Chapter 4, “From Personalized Medicine to Personalized Justice,” contains a diffuse mixture of discussions ranging

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from another overview of molecular diagnostic methods to a description of the use of in vitro lymphocyte toxicity tests to predict in vivo toxicity. However, personalized justice itself is not explicitly defined, nor is a consensus opinion presented on how the legal system may succeed or fail in dealing with pharmacogenetic issues. On the whole, however, most of the chapters in the subsequent sections that detail the pharmacogenetics of specific drugs and drug classes are excellently balanced overviews of clinical, mechanistic, interpretive, and practical assay testing information that should be invaluable in informing decision-making processes on current and future test implementation

for laboratory managers, clinicians, and hospital administrators. An appealing feature of the book is the use of real-life examples and case studies to illustrate the concepts presented. Another notable and refreshing strength of selected chapters is their detailed and practical descriptions of how pharmacogenetic testing may be used in conjunction with other modalities for monitoring clinical efficacy and of the potential pitfalls and barriers that exist for the effective implementation of pharmacogenetic testing. Two prime examples are Chapters 7 and 8, on thiopurine methyltransferase testing for thiopurine administration and genetically enabled warfarin prescribing, respectively. In the latter

chapter, the description of new oral anticoagulant agents such as dabigatran and rivaroxaban provides a timely illustration of how pharmacogenetic testing for a given drug must constantly compete in the marketplace with new discoveries in both therapeutic and diagnostic alternatives to genetically enabled drug prescribing. These new agents appear to be equivalent to warfarin in potency, but they are not subject to pharmacogenetic variation and do not require blood coagulation time (international normalized ratio) monitoring. Finally, it is refreshing to note that certain chapters, such as Chapter 9, on antiplatelet therapies, avoid the previously common pitfall of predicting significant future utility of

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pharmacogenetic testing even though the evidence accumulated to date is lacking or weak. Overall, this monograph provides a useful and current source of information for professionals in clinical and diagnostic practice who are faced with the competing pressures of a public hungry for perfectly personalized medicine and a health-care profession that needs to understand the basis of the variations that occur and to translate that information into usable and economically viable tests in the circumstances in which it is clearly indicated. CONFLICT OF INTEREST The author declared no conflict of interest. © 2011 ASCPT

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