Book Review

Antiangiogenic Cancer Therapy

N Engl J Med 2008; 359:545-546July 31, 2008

Article

Antiangiogenic Cancer Therapy
Edited by Darren W. Davis, Roy S. Herbst, and James L. Abbruzzese. 841 pp., illustrated. Boca Raton, FL, CRC Press, 2008. $199.95. ISBN: 978-0-8493-2799-5

This year began with the death of Judah Folkman, an enormous blow to the medical and scientific communities. It was in the Journal, in 1971, that Folkman published the seminal framework for his ideas about what is now known as tumor angiogenesis. The importance of angiogenesis in preclinical cancer models was reproduced in hundreds of laboratories worldwide, culminating in 2004 in the first antiangiogenic therapy approved by the Food and Drug Administration (FDA) to treat cancer, bevacizumab (Avastin, Genentech). Although this monoclonal antibody is the first in what we hope will be a useful class of therapeutics, antiangiogenic monotherapy has not produced the dramatic results that were once expected.

With few exceptions, solid tumors are driven by proangiogenic mediators such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. Such factors are intricately related to tumor biology in a manner that is still not fully understood. Antiangiogenic Cancer Therapy is a timely and worthwhile study of the complexities of the clinical application of angiogenesis inhibitors. This book, probably the most comprehensive of its kind, is nicely tempered in its assessments of both the triumphs of antiangiogenic tumor therapy and the gaps in knowledge that impede further successful treatments. Particularly evident is the need for biomarkers and for a better understanding of the molecular mechanisms at work, as antiangiogenic therapy has its effects on both endothelial and perivascular cell lineages.

The editors and contributors of this book — including Folkman, who discusses tumor dormancy and the angiogenic switch — are leaders in the field. The chapters are divided into four parts, beginning with a comprehensive background section on angiogenic factors and tumor biology that transitions into the second section, which contains discussions of molecular targets suitable for this form of cancer therapy. The descriptions of methods for identifying new molecular targets include a nice discussion of genomic and proteomic-based techniques. Part III, which mostly highlights the drug-approval and regulatory process, includes chapters about ongoing research, including discussions of surrogate biomarkers of antiangiogenic efficacy. The last part of the book is an in-depth analysis of current issues concerning the use of antiangiogenic agents for specific malignancies.

A particular strength of this book is its “bench-to-bedside” treatment of anticancer agents. It guides the reader from each seminal finding to its relevance for the growth factor receptor, cell type, and disease. Excellent chapters deal with techniques for the identification of novel antiangiogenic targets and offer a primer on how new therapies gain approval through FDA oversight. Also of particular interest is the discussion of the use of multimodal approaches to study the effects of anti-VEGF in normalizing the vasculature of rectal cancer. This exciting work raises questions on the role of mural cells (vascular smooth-muscle cells and pericytes) in the effect observed with antiangiogenic therapy. Although the text is thorough in the area of biologic therapies (antibodies, peptides, and viruses), less depth is afforded to the design of small-molecule inhibitors (which will probably not be missed by most readers).

The topics covered in Antiangiogenic Cancer Therapy are well chosen and present the reader with balanced discussions of basic principles in vascular biology and ongoing investigations in this area. This authoritative book should be required reading for anyone interested in tumor angiogenesis.

Joshua I. Greenberg, M.D.
David A. Cheresh, Ph.D.
University of California, San Diego, La Jolla, CA 92093
jigreenberg@ucsd.edu