Patient Derived Tumor Xenograft Models - 1st Edition - ISBN: 9780128040102, 9780128040614

Patient Derived Tumor Xenograft Models

1st Edition

Promise, Potential and Practice

Editors: Rajesh Uthamanthil Peggy Tinkey Elisa de Stanchina
eBook ISBN: 9780128040614
Paperback ISBN: 9780128040102
Imprint: Academic Press
Published Date: 25th October 2016
Page Count: 486
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Description

Patient Derived Tumor Xenograft Models: Promise, Potential and Practice offers guidance on how to conduct PDX modeling and trials, including how to know when these models are appropriate for use, and how the data should be interpreted through the selection of immunodeficient strains.

In addition, proper methodologies suitable for growing different type of tumors, acquisition of pathology, genomic and other data about the tumor, potential pitfalls, and confounding background pathologies that occur in these models are also included, as is a discussion of the facilities and infrastructure required to operate a PDX laboratory.

Key Features

  • Offers guidance on data interpretation and regulatory aspects
  • Provides useful techniques and strategies for working with PDX models
  • Includes practical tools and potential pitfalls for best practices
  • Compiles all knowledge of PDX models research in one resource
  • Presents the results of first ever global survey on standards of PDX development and usage in academia and industry

Readership

Laboratory animal scientists, veterinarians, laboratory animal technicians and scientists working with the model, including cancer research scientists and pharmaceutical scientists

Table of Contents

  • List of Contributors
  • Biographies
  • Foreword
  • Preface
  • Section I. Mouse Xenograft Models of Cancer
    • Chapter 1. PDX Models: History and Development
      • Introduction
      • History of PDX Mouse Models
      • Resurgence of PDX Models
      • Applications of PDX Models
    • Chapter 2. History of Mouse Cancer Models
      • Introduction
      • Immunodeficient Mouse Models
      • History of Mouse Models in Cancer Research
      • Xenografts
      • Future Directions of Murine Models in Basic Research
    • Chapter 3. Challenges and Limitations of Mouse Xenograft Models of Cancer
      • Introduction
      • Consider the Source: Cell Lines as Xenografts
      • Consider the Host: Mouse Xenograft Models
      • Consider the Method: Technique and Analysis of Xenograft Models
      • Conclusion
    • Chapter 4. Tumor Heterogeneity
      • Introduction
      • Heritable Sources of Heterogeneity
      • Context-Dependent Sources of Heterogeneity
      • Evolution of the Cancer Stem Cell Model
      • Clinical Implications of Tumor Heterogeneity
      • PDX Models to Preserve Tumor Heterogeneity
    • Chapter 5. Immunodeficient Mice: The Backbone of Patient-Derived Tumor Xenograft Models
      • Introduction
      • Introduction to the Immune System and Antitumor Immunity
      • SCID-Interleukin-2 Receptor Common Gamma Chain (IL2rg) Null Mice
      • Limitations of Using Immunodeficient Mice as Patient-Derived Xenograft Hosts
    • Chapter 6. Humanized Mice and PDX Models
      • Introduction
      • History of Humanized Mice
      • Reconstitution of the Human Immune System in Immunodeficient Mice
      • Limitations of Humanized Mice Models for Cancer Biology
      • Utility of Humanized Mice in Cancer
      • Future Directions
  • Section II. Components of a PDX Program
    • Chapter 1. Regulations of Patient-Derived Xenografts
      • Regulations Surrounding the Procurement of Human Tissues for Research
      • Occupational and Environmental Health Regulations When Working With PDX Tumors
      • Regulatory Aspects of Animal Use for the Development and Evaluation of PDX Tumors
    • Chapter 2. Acquisition and Storage of Clinical Samples to Establish PDX Models
      • Coordination
      • Screening
      • Collection
      • Distribution and Storage
    • Chapter 3. Methodologies for Developing and Maintaining Patient-Derived Xenograft Mouse Models
      • Sample Processing Techniques
      • Implantation Techniques
      • Tumor Take Rate and Growth Rate
      • Propagation and Preservation
    • Chapter 4. Pathology of Patient-Derived Xenograft Tumors
      • Introduction
      • The Various Domains of Application of Pathology in Patient-Derived Xenograft Studies
      • Technical Considerations
      • Suggested Schedules for Histological Analyses
      • Pitfalls
      • Conclusion
    • Chapter 5. Genetic Profiling of Tumors in PDX Models
      • Introduction
      • Laboratory Techniques
      • Bioinformatic Techniques
    • Chapter 6. Running a PDX Core Laboratory or a PDX Support Program
      • Infrastructure
      • Personnel
      • Data Storage and Management
      • Cost Analysis Considerations
    • Chapter 7. Veterinary Care
      • Introduction
      • Pathogens and Opportunists
      • Mouse Strain–Specific Diseases
      • Humanized Mice and Graft-Versus-Host Disease
      • Radiation
      • Cytotoxic Chemotherapeutic Drugs and Treatments
      • Engrafted Tumors
      • Conclusion
    • Chapter 8. Occupational Health and Safety
      • Introduction
      • PDX Mouse Models: Unique Occupational Health Concerns
      • Infectious Agents of Concern
      • Potential Infections Agents
  • Section III. PDX Models for Tumors of Various Organ Systems
    • Chapter 1. Pediatric and Adult Brain Tumor PDX Models
      • Background
      • Methodologies and Models
      • Tumor Biology
      • Genomic Characterization
    • Chapter 2. Patient-Derived Xenograft Models of Prostate Tumors
      • Background/Overview
      • Methodology and Models
      • Tumor Biology
      • Preclinical/Clinical Applications
      • Future/Challenges
      • Conclusion
    • Chapter 3. Patient-Derived Xenograft Model of Pancreatic Cancer
      • Background and Significance
      • Methodology and Models
      • Future and Challenges
    • Chapter 4. Modeling Breast Cancer Heterogeneity With Patient-Derived Xenografts
      • Background
      • Methodology and Models
      • Tumor Biology
      • Preclinical Utility
      • Challenges and Future Directions
      • Conclusion
    • Chapter 5. Patient-Derived Xenograft Models of Ovarian/Gynecologic Tumors
      • Background
      • Methodology and Models
      • Tumor Biology
      • Preclinical/Clinical Applications
      • Future/Challenges
      • Conclusion
    • Chapter 6. Patient-Derived Xenografts From Lung Cancer and Their Potential Applications
      • Background
      • Methodologies and Models
      • Tumor Biology
      • Applications of PDXs for Preclinical and Clinical Studies
      • Challenges and Perspectives
      • Conclusion
    • Chapter 7. PDX Models of Colorectal Tumors
      • Background and Overview
      • Methodology and Models
      • Tumor Biology
      • Preclinical and Clinical Applications
      • Future and Challenges
      • Conclusions
    • Chapter 8. Patient-Derived Tumor Xenografts in Hematologic Disorders
      • Overview and Classification of Hematopoietic and Lymphoid Tissue Tumors
      • In Vivo Models of Hematologic Disorders
      • The Role of Patient-Derived Tumor Xenografts in the Study of Lymphoproliferative Disorders
      • Conclusions
    • Chapter 9. Patient-Derived Xenografting of Human Melanoma
      • Background and Overview
      • Methodology and Models
      • Tumor Biology
      • Preclinical Applications: Use of PDX Melanomas to Model Patient Outcomes
      • Future/Challenges
    • Chapter 10. Advances in Organoid Culturing of Patient-Derived Tumors
      • Background
      • The History of Organoid Cancer Models
      • Conditional Reprogrammed Cells
      • Benign Organoid Cultures
      • Cancer Organoid Cultures
      • Prostate Cancer Organoids
      • Pancreas Cancer Organoids
      • Colorectal Cancer Organoids
      • Lung Cancer Conditional Reprogrammed Cells
      • Future Directions
  • Section IV. PDX Models in Cancer Research and Therapy Around the World
    • Chapter 1. Global Practices in PDX Programs
      • The Survey
      • PDX Programs: A Global Snapshot
      • Current Practices in Academic PDX Programs
      • From Academia to Commercialization
      • A Successful PDX Program
      • Recommendations for Improving Current PDX Practices
      • Summary and Concluding Comments
    • Chapter 2. Role of Companies and Corporations in the Development and Utilization of PDX Models
      • Introduction
      • PDX Inventory and Tumor Samples
      • Practice and Protocols
      • Model Development, Challenges, and Future Directions
      • Interview With Company Representatives Regarding Challenges and Future Directions in PDX Development
      • Summary and Concluding Comments
      • Appendix 1. Additional Information on Some Companies Providing and Supporting PDX Model Development
  • Section V. Challenges & Future of PDX Models
    • Chapter 1. Patient-Derived Tumor Xenograft: Present and Future Challenges and Applications
      • Introduction
      • Technical Improvements
      • PDX Molecular Characterization
      • Innovative PDX Derivative Models
      • The Host (Mouse) Aspect of PDX Models
      • Clinical Trials and Data Reporting
      • Current and Future Accessibility of PDX Models
  • Index

Details

No. of pages:
486
Language:
English
Copyright:
© Academic Press 2017
Published:
Imprint:
Academic Press
eBook ISBN:
9780128040614
Paperback ISBN:
9780128040102

About the Editor

Rajesh Uthamanthil

Rajesh Uthamanthil

Dr. Rajesh Uthamanthil is the director of Comparative Medicine program at Fred Hutchinson Cancer Research Center, Seattle, WA. He received Doctorate in Veterinary Medicine and Veterinary Sciences from Kerala Agricultural University, PhD in Comparative Biosciences from the University of Wisconsin Madison and completed a post doctoral fellowship at Rice University. Dr. Uthamanthil has more than 16 years of experience in animal models of human disease, most of it focused on cancer.

Dr. Uthamanthil also directs the PDX core that support studies using PDX models at Fred Hutchinson Cancer Research Center. Dr. Uthamanthil has more than 20 peer reviewed publications in the area of translational research, has authored/co-authored two book chapters and has made more than 30 presentations in national and international conferences meetings.

Affiliations and Expertise

Director, Comparative Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Peggy Tinkey

Peggy Tinkey

Dr. Peggy Tinkey received degrees in Veterinary Science and Veterinary Medicine from Texas A&M University, completed a postdoctoral fellowship in Pathology at Baylor College of Medicine and is a Diplomate of the American College of Laboratory Animal Medicine. She is a Professor of Comparative Medicine and Chairman of the Department of Veterinary Medicine and Surgery at the University of Texas M.D. Anderson Cancer Center, where she directs the animal research program

Dr. Tinkey has extensive experience in animal models of cancer, with an emphasis of mouse cancer models that includes genetically engineered and mutant mouse models, cell line xenograft models, and patient-derived xenograft models. She has published over 25 peer-reviewed manuscripts and book chapters on animal cancers and cancer models. She combines her expertise in animal models with extensive experience in regulatory medicine and has served on the UTMDACC institutional animal care and use and biosafety committees for more than 20 years.

Affiliations and Expertise

Professor, Department of Veterinary Medicine and Surgery,The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

Elisa de Stanchina

Elisa de Stanchina

Dr. Elisa de Stanchina is the Director of the MSKCC Antitumor Assessment Core Facility, and over the past 8 years has overseen its evolution into a state-of-the-art “Mouse Hospital” that fosters preclinical drug development and coordinates efforts from basic scientists and clinicians to ensure that mouse trials effectively mimic treatment plans of human patients. She is an Associate Lab Member in the Molecular Pharmacology and Chemistry Program at Memorial Sloan Kettering Cancer Center (MSKCC). Her lab works closely with investigators to establish mouse models of cancer and has developed one of the largest Academic PDX core support programs in the U.S., with an extensive bank of clinically annotated models available to MSKCC Investigators and their collaborators. Her work has resulted in over 65 publications in prestigious peer-reviewed journals and she has recently authored one of the chapters in the new edition of the “Mouse Models of Cancer” book by CSHL Press.

Affiliations and Expertise

Director, Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, NY, USA