Animal Models in Cancer Drug Discovery brings forward the most cutting-edge developments in tumor model systems for translational cancer research. The reader can find under this one volume virtually all types of existing and emerging tumor models in use by the research community. This book provides a deeper insight on how these newer models could de-risk modern drug discovery. Areas covered include up to date information on latest organoid derived models and newer genetic models. Additionally, the book discusses humanized animal tumor models for cancer immunotherapy and how they leverage personalized therapies. The chapter on larger animal, canine models and their use in and their use in pre-investigational new drug (pre-IND) development makes the volume unique. Unlike before, the incorporation of several simplified protocols, breeding methodologies, handling and assessment procedures to study drug intervention makes this book a must read. Animal Models in Cancer Drug Discovery is a valuable resource for basic and translational cancer researchers, drug discovery researchers, contract research organizations, and knowledge seekers at all levels in the biomedical field.

Beverly A. Teicher and a panel of leading experts comprehensively describe for the first time in many years the state-of-the-art in animal tumor model research. The wide array of models detailed form the basis for the selection of compounds and treatments that go into clinical testing of patients, and include syngeneic models, human tumor xenograft models, orthotopic models, metastatic models, transgenic models, and gene knockout models. Synthesizing many years experience with all the major in vivo models currently available for the study of malignant disease, Tumor Models in Cancer Research provides preclinical and clinical cancer researchers alike with a comprehensive guide to the selection of these models, their effective use, and the optimal interpretation of their results.

This open access book presents recent advances in the pure sciences that are of significance in the quest for alternatives to the use of animals in research and describes a variety of practical applications of the three key guiding principles for the more ethical use of animals in experiments – replacement, reduction, and refinement, collectively known as the 3Rs. Important examples from across the world of implementation of the 3Rs in the testing of cosmetics, chemicals, pesticides, and biologics, including vaccines, are described, with additional information on relevant regulations. The coverage also encompasses emerging approaches to alternative tests and the 3Rs. The book is based on the most informative contributions delivered at the Asian Congress 2016 on Alternatives and Animal Use in the Life Sciences. It will be of value for those working in R&D, for graduate students, and for educators in various fields, including the pharmaceutical and cosmetic sciences, pharmacology, toxicology, and animal welfare. The free, open access distribution of Alternatives to Animal Testing is enabled by the Creative Commons Attribution license in International version 4: CC BY 4.0.

Unravelling the intricate cell signalling networks and their significance in cancer poses major intellectual challenge. Keeping this in mind, the book aims at understanding the mechanism of action of different proteins and their complexes in the cancer signalling pathways. Hence, the proposed book that comprises 20 chapters provides a comprehensive introduction on cell signalling, its alterations in cancer, molecules that have been popular targets as well as the ones that are emerging as targets. In addition, it discusses different forms of therapy that are coming up for its treatment. Other than that, a major portion of the book is focused on studying different disciplines at the interface of biology and other areas of science that are being used to understand cancer biology in depth.

Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.

The laboratory mouse is an important model for addressing questions in cancer biology. In recent years, the questions have become more refined, and mouse models are increasingly being used to develop and test cancer therapeutics. Thus, the need for more sophisticated and clinically relevant mouse models has grown, as has the need for innovative tools to analyze and validate them. This laboratory manual provides cutting-edge methods for generating and characterizing mouse models that accurately recapitulate many features of human cancer. The contributors describe strategies for producing genetic models, including transgenic germline models, gene knockouts and knockins, and conditional and inducible systems, as well as models derived using transposon-based insertional mutagenesis, RNA interference, viral-mediated gene delivery, and chemical carcinogens. Tissue recombination, organ reconstitution, and transplantation methods to develop chimeric, allograft, and xenograft models are covered. Approaches to characterize tumor development, progression, and metastasis in these models using state-of-the-art imaging, histopathological, surgical, and other techniques are also included. Other chapters cover the use of mouse models to test and optimize drugs in pre-, co-, and post-clinical trials. An appendix specifically addresses the use of mouse cancer models in translational studies and the integration of mouse and human clinical investigations. This manual is therefore an indispensable laboratory resource for all researchers, from the graduate level upwards, who study cancer and its treatment.

Animal Models for the Study of Human Disease identifies important animal models and assesses the advantages and disadvantages of each model for the study of human disease. The first section addresses how to locate resources, animal alternatives, animal ethics and related issues, much needed information for researchers across the biological sciences and biomedicine.The next sections of the work offers models for disease-oriented topics, including cardiac and pulmonary diseases, aging, infectious diseases, obesity, diabetes, neurological diseases, joint diseases, visual disorders, cancer, hypertension, genetic diseases, and diseases of abuse. - Organized by disease orientation for ease of searchability - Provides information on locating resources, animal alternatives and animal ethics - Covers a broad range of animal models used in research for human disease

The way a cell undergoes malignant transformation should meet their capacity of surviving in the microenvironment of the organ where the cancer will develop. Metabolic adaptation is for sure one of the criteria that must be accomplished, driven by metabolic plasticity that allows the adaptation of cancer cells to the availability of energy and biomass sources that will sustain cell survival and proliferation. Each human organ has a particular microenvironment which depends on several cell types and in some cases also on symbiotic microorganisms. These biological partners are constantly sharing organic compounds and signaling molecules that will control mitogenesis, cell death and differentiation, accounting for the organ's function. Nevertheless, cancer cells are capable of taking advantage of this metabolic and signaling microenvironmental dynamics. In this book, we intend to present the different components of the microenvironment driving the metabolic fitness of cancer cells. The metabolic changes required for establishing a tumor in a given microenvironment and how these metabolic changes limit the response to drugs will generally be the major items addressed. It is important to mention not only aspects of the microenvironment that stimulate metabolic changes and that select better adapted tumor cells, but also how this regulation of cell plasticity is made. Thus, the signaling pathways that orchestrate and are orchestrated throughout this panoply of metabolic rearrangements will also be addressed in this book. The subjects will be presented from the conceptual point of view of the cross-cancer mechanisms and also particularizing some models that can be examples and enlightening within the different areas.

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.