Experienced cancer researchers from pharmaceutical companies, government laboratories, and academia comprehensively review and describe the arduous process of cancer drug discovery and approval. They focus on using preclinical in vivo and in vitro methods to identify molecules of interest, detailing the targets and criteria for success in each type of testing and defining the value of the information obtained from the various tests. They also define each stage of clinical testing, explain the criteria for success, and outline the requirements for FDA approval. A companion volume by the same editor (Cancer Therapeutics: Experimental and Clinical Agents) reviews existing anticancer drugs and potential anticancer therapies. These two volumes in the Cancer Drug Discovery and Development series reveal how and why molecules become anticancer drugs and thus offer a blueprint for the present and the future of the field.
This unique volume traces the critically important pathway by which a "molecule" becomes an "anticancer agent. " The recognition following World War I that the administration of toxic chemicals such as nitrogen mustards in a controlled manner could shrink malignant tumor masses for relatively substantial periods of time gave great impetus to the search for molecules that would be lethal to specific cancer cells. Weare still actively engaged in that search today. The question is how to discover these "anticancer" molecules. Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval, Second Edition describes the evolution to the present of preclinical screening methods. The National Cancer Institute's high-throughput, in vitro disease-specific screen with 60 or more human tumor cell lines is used to search for molecules with novel mechanisms of action or activity against specific phenotypes. The Human Tumor Colony-Forming Assay (HTCA) uses fresh tumor biopsies as sources of cells that more nearly resemble the human disease. There is no doubt that the greatest successes of traditional chemotherapy have been in the leukemias and lymphomas. Since the earliest widely used in vivo drug screening models were the murine L 1210 and P388 leukemias, the community came to assume that these murine tumor models were appropriate to the discovery of "antileukemia" agents, but that other tumor models would be needed to discover drugs active against solid tumors.
This unique volume traces the critically important pathway by which a "molecule" becomes an "anticancer agent. " The recognition following World War I that the administration of toxic chemicals such as nitrogen mustards in a controlled manner could shrink malignant tumor masses for relatively substantial periods of time gave great impetus to the search for molecules that would be lethal to specific cancer cells. Weare still actively engaged in that search today. The question is how to discover these "anticancer" molecules. Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval, Second Edition describes the evolution to the present of preclinical screening methods. The National Cancer Institute's high-throughput, in vitro disease-specific screen with 60 or more human tumor cell lines is used to search for molecules with novel mechanisms of action or activity against specific phenotypes. The Human Tumor Colony-Forming Assay (HTCA) uses fresh tumor biopsies as sources of cells that more nearly resemble the human disease. There is no doubt that the greatest successes of traditional chemotherapy have been in the leukemias and lymphomas. Since the earliest widely used in vivo drug screening models were the murine L 1210 and P388 leukemias, the community came to assume that these murine tumor models were appropriate to the discovery of "antileukemia" agents, but that other tumor models would be needed to discover drugs active against solid tumors.
There are many steps on the road from discovery of an anticancer drug to securing its final approval by the Food and Drug Administration. In this thoroughly updated and expanded second edition of the Handbook of Anticancer Pharmacokinetics and Pharmacodynamics, leading investigators synthesize an invaluable overview of the experimental and clinical processes of anticancer drug development, creating a single indispensable reference that covers all the steps from the identification of cancer-specific molecular targets to screening techniques and the development and validation of bioanalytical methods to clinical trial design and all phases of clinical trials. The authors have included new material on phase 0 trials in oncology, organ dysfunction trials, drug formulations and their impact on anticancer drug PK/PD including strategies to improve drug delivery, pharmacogenomics and cancer therapy, high throughput platforms in drug metabolism and transport pharmacogenetics, imaging in drug development and nanotechnology in cancer. Authoritative and up-to-date, Handbook of Anticancer Pharmacokinetics and Pharmacodynamics, 2nd Edition provides in one comprehensive and highly practical volume a detailed step-by-step guide to the successful design and approval of anticancer drugs. Road map to anticancer drug development from discovery to NDA submission Discussion of molecular targets and preclinical screening Development and validation of bioanalytical methods Chapters on clinical trial design and phase 0, I, II, III clinical trials Pharmacokinetics, pharmacodynamics, pharmacogenomics, and pharmacogenetics of anticancer agents Review of the drug development process from both laboratory and clinical perspectives New technological advances in imaging, high throughput platforms, and nanotechnology in anticancer drug development
Perhaps no area of pharmacology has progressed further or faster than that of anticancer drugs. With this concise and informative resource, you'll explore the full spectrum of anticancer drug evolution -- from research and development, through clinical trials, to licensure and utilization.
Here in a single source is a complete spectrum of ideas on the development of new anticancer drugs. Containing concise reviews of multidisciplinary fields of research, this book offers a wealth of ideas on current and future molecular targets for drug design, including signal transduction, the cell division cycle, and programmed cell death. Detailed descriptions of sources for new drugs and methods for testing and clinical trial design are also provided. One work that can be consulted for all aspects of anticancer drug development Concise reviews of research fields, combined with practical scientific detail, written by internationally respected experts A wealth of ideas on current and future molecular targets for drug design, including signal transduction, the cell division cycle, and programmed cell death Detailed descriptions of the sources of new anticancer drugs, including combinatorial chemistry, phage display, and natural products Discussion of how new drugs can be tested in preclinical systems, including the latest technology of robotic assay systems, cell culture, and experimental animal techniques Hundreds of references that allow the reader to access relevant scientific and medical literature Clear illustrations, some in color, that provide both understanding of the field and material for teaching
Cancer Pharmacology: An Illustrated Manual of Anticancer Drugs provides a one-stop guide to the essential basic and clinical science of all the effective, life-prolonging drug therapies in oncology. From traditional cytotoxic agents to targeted genomic, epigenomic, hormonal, and immunotherapeutic agents, this book covers the staggering advances in cancer pharmacology that are propelling new standards of care for common and uncommon malignancies. Beautifully illustrated throughout, each chapter contains visually engaging figures detailing the tumor microenvironment, chemical structures of agents, pharmacodynamics, pharmacokinetics, pharmacogenomic, and molecular properties of the various agents, and their mechanisms of action. As the first illustrated book of its kind, this highly visual text uses a uniform approach to each cancer drug class and agent presented in the book, and covers alkylating agents, antimetabolites, antimitotics, epigenetic modulators, hormonal agents, targeted therapies, monoclonal antibodies, immunotherapeutic agents, and much more. Flow diagrams, clinical tables, and bulleted text further explain important information pertaining to each cancer drug class including their indications, mechanisms of action, potential adverse reactions, dosing and dose adjustments, and safety monitoring. Organized in an easyto- digest format and replete with detailed images, clinical pearls, and end of chapter Q&As, this evidence-based reference presents all major classes, agents, targets, and approaches to cancer pharmacotherapy. Whether you are a trainee, a clinical scientist, or a clinician in practice, the book is an ideal reference. It presents challenging information in an instructional way, illustrates key concepts for ease of retention, and poses tough questions so readers can problem solve potential scenarios and test their pharmacologic acumen. Written by leading experts in oncopharmacology, this first-of-its kind manual is a “must have” for anyone involved in the basic, translational, or clinical aspects of oncology and hematology including clinicians, pharmacists, nurses, and trainees. KEY FEATURES: Includes visual depictions of chemical structures, pharmacokinetics, pharmacodynamics, and pharmacogenomics associated with each class of agents Describes how chemotherapy, targeted therapy, immunotherapy, and hormonal therapy work and why they are expected to work adjuvantly, neoadjuvantly, and in combination with other modalities Over 100 highly stylized images and numerous comprehensive tables Covers challenges related to drug development, drug approval, and regulatory issues in relation to anticancer treatments All chapters conclude with clinical pearls and detailed clinical Q&As with descriptive rationales Purchase includes access to the ebook for use on most mobile devices or computers
Cancer drug discovery has been and continues to be a process of ingenuity, serendip ity, and dogged determination. In an effort to develop and discover better therapies against cancer, investigators all over the world have increased our knowledge of cell biology, biochemistry, and molecular biology. The goal has been to define therapeuti cally exploitable differences between normal and malignant cells. The result has been an increased understanding of cellular and whole-organism biology and an increased respect for the flexibility and resiliency ofbiologically systems. Thus, as some new therapeutic targets have been defined and new therapeutic strategies have been attempted, so have some new biological hurdles resulting from tumor evasion of the intended therapeutic attack been discovered. Historically, anticancer drugs have originated from all available chemical sources. Synthetic molecules from the chemical industry, especially dyestuffs and warfare agents, and natural products from plants, microbes, and fungi have all been potential sources of pharmaceuticals, including anticancer agents. There is no shortage of molecules; the challenge has been and continues to be methods of identifying molecules that have the potential to be therapeutically important in human malignant disease. "Screening" remains the most important and most controversial method in cancer drug discovery. In vitro screens have generally focused on cytotoxicity and have identified several highly cytotoxic molecules. Other endpoints available in vitro are inhibition of proliferation, 3 inhibition of [ H]thymidine incorporation into DNA and various viability assays, based most frequently on dye exclusion or metabolism.
