CNS Cancer Models

CNS Cancer Models is a 1284-page book covering the fast-growing advances in basic and translational neuro-oncology research. Three different sections address “Animal Models for Central Nervous Tumors,” “Prognostic Factors and Biomarkers,” and “Therapeutic Targets and Targeting Approaches.” Given this structure, it differs from the many other textbooks covering neoplasms in the brain (which are most often organized by pathology) by strictly focusing on the underlying pathways and mechanisms and how they can be utilized in the laboratory setting. Van Meir, PhD, was able to recruit outstanding researchers and physician scientists as contributors. All essays in CNS Cancer Models focus almost entirely on high-grade glioma. Unfortunately, other important malignancies, such as ependymomas and meningiomas, are not covered in depth. Topics that might have deserved a chapter include the Hedgehog pathway and underlying mechanisms of meningiomas or leptomeningeal disease. The first part of the book describes 13 different animal models. Indeed, at 13 chapters and 282 pages, this section alone is in itself a comprehensive textbook on the topic of animal models. It is comprehensive as well as forward-looking. Several of the chapters are included for the sake of completeness, since many of the models described in several chapters are no longer in widespread use. The second part of the book focuses on potentially prognostic factors and biomarkers. The 15 chapters highlight clinically relevant mechanisms that influence the development of high-grade glioma. Relatively short and concise chapters describe signaling pathways involved in brain tumors such as p53 and the PTEN/PI3 kinase pathway as well as brain tumor angiogenesis mechanisms and brain tumor and cerebrospinal fluid profiling. The chapter about the p53 pathway alterations involved in brain tumors describes in a clear and precise fashion the complex underlying mechanism that drives tumor growth by explaining the basic functions of the p53 family, its intracellular and microenvironmental functions, and the consequences of mutations. The chapter closes by highlighting mutant p53 as a potential therapeutic target. Another well-written chapter covers the proteomic discovery of biomarkers in the cerebrospinal fluid of brain tumor patients and might serve as an informative primer on this emerging topic in neuro-oncology. Other chapters, however, such as the section on epigenetic profiling, require substantial background knowledge upfront in order to fully appreciate the complex details covered in the section. Very contemporary work, such as the exploding field of micro-RNA, is well covered, not just with regard to a historical review but also with a discussion of the promise of micro-RNA as a therapeutic. The third part of the book concentrates on therapeutic targets and targeting approaches in neuro-oncology. This section builds on the pathways and mechanisms discussed earlier in the book. Topics range from an introductory chapter on targeting brain tumor vasculature to how to apply different virus vectors and stem cells to target glioma growth. Many of the chapters are quick overviews of their respective fields, and several do little to place their topic in the context of other molecular approaches. The single-target approach, as we know, has not been borne out well in the clinic, so this synthesis is missing. Along these lines, though, one of the standout chapters is a thoughtful and detailed discussion of multi-targeting and combinatorial therapy, which begins to describe the dynamic nature of signaling cascades perturbed by single-agent blockades. The dynamic nature of signaling cascades and their response to inhibition has not been widely addressed. In this chapter, reviews of the Akt-mTOR feedback loops, the EGFRviii/PTEN network, and RAS-PI3k crosstalk provide brief but important discussions on the interconnectedness of and dynamic interactions between pathways we often think of as unidirectional stick-figure diagrams but that are actually multidirectional interactive webs. What would have made a major contribution, in our opinion, is a chapter on the emerging field of systems biology, where the preceding major works on individual topics could have been reviewed in some context of the whole organ that brain tumors represent. The compact page size format of the book is rather unfortunate and does not help to improve readability and understanding, especially at over 1,200 pages! The figures and graphics could be improved, given the small size of the pages and the black and white print, to expand understanding and explain the complex natures described in the text. At times, explanations run over several pages, and the color plates displayed in two separate sections in the middle of the book are rather small and difficult to read. The same applies to the black and white figures, which at times are just too tiny because of the small format size of the book. The clear structure of each chapter and the table of contents following the abstract of each section increase the readability of the book. Even if some newly recognized topics, such as the role of IDH1 in glioma and the Sonic Hedgehog pathway, did not find their way into this first edition, mostly owing to the limitation of the publishing process and the accelerating pace of discovery, the book helps the reader get an extensive overview of targets and pathways in neuro-oncology. It is an excellent and encyclopedic book for translational researchers as well as clinicians who would like to gain a deeper understanding of the underlying mechanisms that drive brain tumors and potential therapies. There are no other currently available works that we are aware of that are so comprehensive yet focused on the promise for translational work in the field of malignant glioma research.