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.
Second-harmonic generation (SHG) microscopy has shown great promise for imaging live cells and tissues, with applications in basic science, medical research, and tissue engineering. Second Harmonic Generation Imaging offers a complete guide to this optical modality, from basic principles, instrumentation, methods, and image analysis to biomedical a
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.
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.
Marten Hofker and Jan van Deursen have assembled a multidisciplinary collection of readily reproducible methods for working with mice, and particularlyfor generating mouse models that will enable us to better understand gene function. Described in step-by-step detail by highly experienced investigators, these proven techniques include new methods for conditional, induced knockout, and transgenic mice, as well as for working with mice in such important research areas as immunology, cancer, and atherosclerosis. Such alternative strategies as random mutagenesis and viral gene transduction for studying gene function in the mouse are also presented.
Biomaterials for 3D Tumor Modeling reviews the fundamentals and most relevant areas of the latest advances of research of 3D cancer models, focusing on biomaterials science, tissue engineering, drug delivery and screening aspects. The book reviews advanced fundamental topics, including the causes of cancer, existing cancer models, angiogenesis and inflammation during cancer progression, and metastasis in 3D biomaterials. Then, the most relevant biomaterials are reviewed, including methods for engineering and fabrication of biomaterials. 3D models for key biological systems and types of cancer are also discussed, including lung, liver, oral, prostate, pancreatic, ovarian, bone and pediatric cancer. This book is suitable for those working in the disciplines of materials science, biochemistry, genetics, molecular biology, drug delivery and regenerative medicine. - Reviews key biomaterials topics, including synthetic biomaterials, hydrogels, e-spun materials and nanoparticles - Provides a comprehensive overview of 3D cancer models for key biological systems and cancer types - Includes an overview of advanced fundamental concepts for an interdisciplinary audience in materials science, biochemistry, regenerative medicine and drug delivery
This book is a compilation of the bench experience of leading experts from various research labs involved in the cutting edge area of research. The authors describe the use of stem cells both as part of the combinatorial therapeutic intervention approach and as tools (disease model) during drug development, highlighting the shift from a conventional symptomatic treatment strategy to addressing the root cause of the disease process. The book is a continuum of the previously published book entitled "Stem Cells: from Drug to Drug Discovery" which was published in 2017.
Tumor progression is driven by mutations that confer growth advantages to different subpopulations of cancer cells. As a tumor grows, these subpopulations expand, accumulate new mutations, and are subjected to selective pressures from the environment, including anticancer interventions. This process, termed clonal evolution, can lead to the emergence of therapy-resistant tumors and poses a major challenge for cancer eradication efforts. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines cancer progression as an evolutionary process and explores how this way of looking at cancer may lead to more effective strategies for managing and treating it. The contributors review efforts to characterize the subclonal architecture and dynamics of tumors, understand the roles of chromosomal instability, driver mutations, and mutation order, and determine how cancer cells respond to selective pressures imposed by anticancer agents, immune cells, and other components of the tumor microenvironment. They compare cancer evolution to organismal evolution and describe how ecological theories and mathematical models are being used to understand the complex dynamics between a tumor and its microenvironment during cancer progression. The authors also discuss improved methods to monitor tumor evolution (e.g., liquid biopsies) and the development of more effective strategies for managing and treating cancers (e.g., immunotherapies). This volume will therefore serve as a vital reference for all cancer biologists as well as anyone seeking to improve clinical outcomes for patients with cancer.
‘The story of oncology is not only fascinating but also contains many accounts of dead ends, chance discoveries, illusions, mistakes and disappointments alongside the few successes.’These words are taken from the introduction to this book. The author, professor emeritus of Medical Oncology, reviews all aspects of the problem of cancer from a historical perspective, from the oldest existing records to the latest scientific and medical advances. It will interest the many people engaged in the treatment of cancer to read how the current therapeutic methods came about, and the book may also provide inspiration for cancer researchers, and for all those directly or indirectly involved with cancer. The layman looking for background information on a particular treatment may find it useful too. The various chapters can be read independently. A glossary and a few explanatory diagrams augment the text.This book grew out of an invitation the author received to lecture on the history of oncology. During his background reading, he discovered that there was no single volume dealing with the entire history of the subject. Fortunately, however, a great deal of information could be found here and there in the literature. As he read, he was struck by the fascinating stories behind many discoveries, and felt impelled to put them together in a single comprehensive account. The results of his labors are presented in this remarkable volume.The author, Prof. D.J.Th. (Theo) Wagener, was head of the department of Medical Oncology at the Radboud University Nijmegen Medical Centre in the Netherlands from 1982 to 2001, chairman of the Educational Committee of the European Society of Medical Oncology (ESMO), a member of the Educational Committee of the American Society of Clinical Oncology (ASCO) and a member of various international scientific working groups, mainly of the European Organization for Research and Treatment of Cancer (EORTC).