Molecular Cancer Therapeutics: Strategies for Drug Discovery and Development
http://www.100md.com
《新英格兰医药杂志》
In this excellent and timely book, George Prendergast has created a primer for academically trained laboratory scientists about the challenges of developing modern drugs. The growing expectation among the public that scientific advances in cancer research should be applied to clinical medicine as rapidly as possible has made it essential for even the most basic-science–oriented researcher to gain some familiarity with how drugs are discovered and developed. Furthermore, the landscape of modern biomedical research is evolving, both in its innate structure and in the types of personnel and institutions that are involved.
New treatments are now rationally designed to target specific aspects of malignant cells, on the basis of our growing molecular understanding of cancer biology. In addition, basic scientific observations that are pharmaceutically relevant are increasingly being made within large research universities and in a growing legion (or shrinking, depending on the economic cycle) of small biotechnology companies. Many of these start-up commercial initiatives are seeded by academic discoveries. In contrast, the resource-intensive process of drug development is traditionally guided by large pharmaceutical companies. This new partnership requires constructive collaboration between experts in basic science and drug development to produce the optimal division of labor.
For the young, academically trained scientist, approaching the complex interface between academics and industry for the first time can be bewildering. Historically, expertise is achieved only after many years of hands-on experience, and comprehensive, well-written reference works in this area are notably lacking. This book ambitiously and successfully fills the void, thereby easing the novice's introduction to the rapidly changing field. The astute recognition of the need for this type of textbook probably derives from the editor's own personal experience as a leader in cancer research.
The book consists of chapters ranging from the general to the specific, which as a whole provide a comprehensive overview of the discovery of anticancer drugs and early preclinical development. By design, the emphasis is on small-molecule therapies, in which the greatest knowledge gap is perceived to exist. A fundamental theme that resonates throughout the book is that targeted therapies are being driven by our growing understanding of cancer genetics. This emphasis serves as a clarion call for implementation of new paradigms and approaches to preclinical and clinical drug development. Excellent general chapters discuss the promise of new molecularly targeted agents, validation of molecular targets, high-throughput screening for lead compounds, animal models, pharmacokinetics and pharmacodynamics, and clinical drug development.
Also excellent is the discussion about intellectual property and the economics of drug development, often mysterious to scientists and clinicians alike. Interspersed with these general topics are highly detailed chapters about specific types of technology that are fundamental to the discovery and development of targeted drugs, such as DNA-and tissue-microarray applications, and about new techniques, such as RNA interference to silence gene expression selectively. Also included are methods with as-yet-unrealized potential, such as protein transduction, which involves the cellular delivery of large macromolecules through receptor-independent pathways. Although the selection of specific topics directly reflects the editor's bias, the rational design underlying the entire work is clearly evident.
The contributors are a diverse group of academic and industry specialists who, for the most part, are well suited to the task, although the quality of individual chapters varies. Most of the shortcomings are minor. For example, the inclusion of an entire chapter on transgenic animal models may be justified by the emphasis on molecular targets, but the total contribution of such models to drug development to date is limited compared with that of traditional xenograft studies in nude mice. Also valuable is the conceptual discussion of pharmacokinetics and toxicology, but the systematic listing of toxic effects of conventional chemotherapy by class of agents is less so. Likewise, the general discussion of methods of high-throughput screening conveys the impressive power of miniaturization, but it could be better simplified for a general audience.
Nonetheless, the need for a reference work such as this has never been greater. As Prendergast states, academic laboratories and small biotechnology companies increasingly provide the "R" in pharmaceutical R&D (research and development), whereas the "D" is supplied by large pharmaceutical companies. By extension, this little book represents the ever-so-important "and" that links research and development together in a logical and thoughtful manner. As such, it is a detailed reference for experts on both sides of the divide, providing a common framework for discussion and collaboration. It is a valuable resource for scientists and clinicians alike who are interested in modern approaches to the development of anticancer therapeutics.
Chris H. Takimoto, M.D., Ph.D.
Cancer Therapy and Research Center
San Antonio, TX 78229
ctakimot@idd.org(George C. Prendergast. 35)
New treatments are now rationally designed to target specific aspects of malignant cells, on the basis of our growing molecular understanding of cancer biology. In addition, basic scientific observations that are pharmaceutically relevant are increasingly being made within large research universities and in a growing legion (or shrinking, depending on the economic cycle) of small biotechnology companies. Many of these start-up commercial initiatives are seeded by academic discoveries. In contrast, the resource-intensive process of drug development is traditionally guided by large pharmaceutical companies. This new partnership requires constructive collaboration between experts in basic science and drug development to produce the optimal division of labor.
For the young, academically trained scientist, approaching the complex interface between academics and industry for the first time can be bewildering. Historically, expertise is achieved only after many years of hands-on experience, and comprehensive, well-written reference works in this area are notably lacking. This book ambitiously and successfully fills the void, thereby easing the novice's introduction to the rapidly changing field. The astute recognition of the need for this type of textbook probably derives from the editor's own personal experience as a leader in cancer research.
The book consists of chapters ranging from the general to the specific, which as a whole provide a comprehensive overview of the discovery of anticancer drugs and early preclinical development. By design, the emphasis is on small-molecule therapies, in which the greatest knowledge gap is perceived to exist. A fundamental theme that resonates throughout the book is that targeted therapies are being driven by our growing understanding of cancer genetics. This emphasis serves as a clarion call for implementation of new paradigms and approaches to preclinical and clinical drug development. Excellent general chapters discuss the promise of new molecularly targeted agents, validation of molecular targets, high-throughput screening for lead compounds, animal models, pharmacokinetics and pharmacodynamics, and clinical drug development.
Also excellent is the discussion about intellectual property and the economics of drug development, often mysterious to scientists and clinicians alike. Interspersed with these general topics are highly detailed chapters about specific types of technology that are fundamental to the discovery and development of targeted drugs, such as DNA-and tissue-microarray applications, and about new techniques, such as RNA interference to silence gene expression selectively. Also included are methods with as-yet-unrealized potential, such as protein transduction, which involves the cellular delivery of large macromolecules through receptor-independent pathways. Although the selection of specific topics directly reflects the editor's bias, the rational design underlying the entire work is clearly evident.
The contributors are a diverse group of academic and industry specialists who, for the most part, are well suited to the task, although the quality of individual chapters varies. Most of the shortcomings are minor. For example, the inclusion of an entire chapter on transgenic animal models may be justified by the emphasis on molecular targets, but the total contribution of such models to drug development to date is limited compared with that of traditional xenograft studies in nude mice. Also valuable is the conceptual discussion of pharmacokinetics and toxicology, but the systematic listing of toxic effects of conventional chemotherapy by class of agents is less so. Likewise, the general discussion of methods of high-throughput screening conveys the impressive power of miniaturization, but it could be better simplified for a general audience.
Nonetheless, the need for a reference work such as this has never been greater. As Prendergast states, academic laboratories and small biotechnology companies increasingly provide the "R" in pharmaceutical R&D (research and development), whereas the "D" is supplied by large pharmaceutical companies. By extension, this little book represents the ever-so-important "and" that links research and development together in a logical and thoughtful manner. As such, it is a detailed reference for experts on both sides of the divide, providing a common framework for discussion and collaboration. It is a valuable resource for scientists and clinicians alike who are interested in modern approaches to the development of anticancer therapeutics.
Chris H. Takimoto, M.D., Ph.D.
Cancer Therapy and Research Center
San Antonio, TX 78229
ctakimot@idd.org(George C. Prendergast. 35)