Oncogene Directed Therapies Cancer Drug Discovery And Development

Prominent investigators and clinicians summarize in a balanced blend of fundamental science, basic research, experimental therapeutics, and early clinical experiences, what is known about oncogenes and oncogenesis, and describe how that knowledge can be used to treat the cancer. The contributors explain how, why, and under what conditions certain proteins acquire the ability to transform eukaryotic cells, and detail the crucial biological consequences of this oncogenic transformation, particularly for cellular mitogenesis, survival, differentiation, migration, proteolysis, or angiogenic competence. Their articles thoroughly explicate the premises, principles, techniques, and approaches to oncogene targeting in various types of human cancer by using signal transduction inhibitors, immunological targeting methods, and antisense gene therapy.

In recent years an entirely new category of anticancer agents has entered the clinic. This class of drugs, the frontrunners of which are Herceptin and Gleevec, are no longer a product of the intuitive and largely empirical explorations that brought about traditional anticancer treatments like chemotherapy. Rather, these new agents have emerged directly from molecular analysis of various cancer-causing genes (oncogenes). In Oncogene-Directed Therapies, prominent investigators and clinicians, several of them pioneers in the field, summarize what is known about oncogenes and oncogenesis-in a balanced blend of fundamental science, basic research, experimental therapeutics, and early clinical experience-and describe how that knowledge can be used to treat the disease. The contributors explain how, why, and under what conditions certain proteins acquire the ability to transform eukaryotic cells, and detail the crucial biological consequences of this oncogenic transformation, particularly for cellular mitogenesis, survival, differentiation, migration, proteolysis, or angiogenic competence. Their articles thoroughly explicate the premises, principles, techniques, and approaches to oncogene targeting in various types of human cancer by using signal transduction inhibitors, immunological targeting methods, and antisense gene therapy. Also included is a review of the results of preclinical and clinical testing of some of today's most advanced therapeutic agents. Unique in perspective and comprehensive in its coverage, Oncogene-Directed Therapies not only integrates for all those engaged in-or simply interested in the cutting-edge of-the war on cancer" the many remarkable recent achievements in our molecular understanding and treatment of these diseases, but also clarifies what directions future research might optimally take, as well as what significant accomplishments might lie ahead."

The reader will discover a comprehensive and multifaceted overview of the history of the development of anticancer drugs deeply influenced by the cell concept of cancer and future directions for the development of new anticancer drugs. First, this book documents the scientific progress in biological science over the last 70 years and the influence this progress had in cancer research. Summaries and charts of important discoveries complete this overview. Furthermore, this book outlines the process of anticancer drug development with a focus on the characteristic drug groups of each era, related to advancements of chemistry and biological sciences. This book also provides brief mechanism of action of drugs, illustrated by comprehensive timelines and conceptual cartoons. This book finally sums up the limitations of the current anticancer drug development and seeks new directions for anticancer drug discovery, considering under the systemic view of cancer.

An integrated overview of cancer drug discovery and development from the bench to the clinic, showing with broad strokes and representative examples the drug development process as a network of linked components leading from the discovered target to the ultimate therapeutic product. Following a systems biology approach, the authors explain genomic databases and how to discover oncological targets from them, how then to advance from the gene and transcript to the level of protein biochemistry, how next to move from the chemical realm to that of the living cell and, ultimately, pursue animal modeling and clinical development. Emerging cancer therapeutics including Ritux an, Erbitux, Gleevec Herceptin, Avastin, ABX-EGF, Velcade, Kepivance, Iressa, Tarceva, and Zevalin are addressed. Highlights include cancer genomics, pharmacogenomics, transcriptomics, gene expression analysis, proteomic and enzymatic cancer profiling technologies, and cellular and animal approaches to cancer target validation.

Billions of dollars are spent every year on research into targeted therapies for cancer. That’s why it’s more than ever crucial for the thousands of scientists working in the field to keep right up to date with the cutting edge. This fascinating collection of material goes a long way to helping them do so, featuring as it does contributions to a crucial international meeting in Italy. The meeting provided a forum for scientists and clinicians working in cancer drug discovery and therapy to share their opinions and experiences. The text here offers readers an overview of diverse approaches, ranging from drug discovery to cellular therapy. Overall, the book addresses the key question of whether ultimately targeted therapy in cancer will be a myth or a reality.

Cancer Drug Design and Discovery, Second Edition is an important reference on the underlying principles for the design and subsequent development of new anticancer small molecule agents. New chapters have been added to this edition on areas of particular interest and therapeutic promise, including cancer genomics and personalized medicine, DNA-targeted agents and more. This book includes several sections on the basic and applied science of cancer drug discovery and features those drugs that are now approved for human use and are in the marketplace, as well as those that are still under development. By highlighting some of the general principles involved in taking molecules through basic science to clinical development, this book offers a complete and authoritative reference on the design and discovery of anticancer drugs for translational scientists and clinicians involved in cancer research. Provides a clinical perspective on the development of new molecularly targeted anticancer agents with the latest and most promising chemotherapeutic approaches Offers a broad view of where the field is going, what tools drug discovery is using to produce new agents and how they are evaluated in the laboratory and clinic Features 6 new chapters devoted to advances in technology and successful anticancer therapies, such as cancer genomics and personalized medicine, DNA-targeted agents, B-Raf inhibitors and more Each chapter includes extensive references to the primary and review literature, as well as to relevant web-based sources

Molecular Cancer Therapeutics covers state-of-the-art strategies to identify and develop cancer drug target molecules and lead inhibitors for clinical testing. It provides a thorough treatment of drug target discovery, validation, and development. The introductory chapters provide an overview of pathways to discovery and development of molecular cancer therapeutics. Subsequent chapters progress from initial stages of drug target discovery to drug discovery, development, and testing in preclinical and clinical models. Topics include drug lead screening, drug-to-lead development, proof-of-concept studies, medicinal chemistry issues, intellectual property concerns, and clinical development. This invaluable reference promotes understanding of steps involved in developing drug leads for industrial partnering and development. It provides an overview of the strategies for discovery and validation of drug target molecules, and discusses cell- and molecule-based drug screening strategies, as well as mouse models for cancer. Coverage also includes how to refine drug leads for suitability in clinical testing, the special issues of clinical testing of molecular-targeted drugs, and intellectual property concerns.

Leading experts summarize and synthesize the latest discoveries concerning the changes that occur in tumor cells as they develop resistance to anticancer drugs, and suggest new approaches to preventing and overcoming it. The authors review physiological resistance based upon tumor architecture, cellular resistance based on drug transport, epigenetic changes that neutralize or bypass drug cytotoxicity, and genetic changes that alter drug target molecules by decreasing or eliminating drug binding and efficacy. Highlights include new insights into resistance to antiangiogenic therapies, oncogenes and tumor suppressor genes in therapeutic resistance, cancer stem cells, and the development of more effective therapies. There are also new findings on tumor immune escape mechanisms, gene amplification in drug resistance, the molecular determinants of multidrug resistance, and resistance to taxanes and Herceptin.