Hepatocellular carcinoma (HCC), the most common form of liver cancer, has become a major global health problem. Although the risk factors for HCC development are well known and great advances have been made through HBV vaccinations, direct-acting antivirals for HCV treatment, and aflatoxin eradication programs, the overall incidence and mortality rates of HCC are still rising. To tackle the burden of HCC, it is essential to understand the principle molecular and cellular processes as well as fundamental clinical challenges. This book provides an overview on several important disease aspects. Chapter 1 reviews recent studies assessing the potential cellular origins of HCC. Chapter 2 describes the newly discovered regulatory roles of the tumor microenvironment on tumor growth and progression. Chapters 3 and 4 outline the most commonly used in vitro systems and animal models of chronic liver disease and HCC in detail. Chapter 5 provides an overview of metabolic reprogramming and dysregulation of lipid metabolism as a newly recognized hallmark of HCC. Chapter 6 details the currently accepted standards and challenges for the surgical management of HCC, while Chapter 7 provides an overview of the recent developments in the field of tyrosine kinase inhibitors. Chapter 8 discusses multidrug resistance to chemotherapy and potential approaches to overcome this clinical obstacle. The book, written by experts from several countries, addresses each topic in sophisticated detail. It will be a valuable resource for clinicians and investigators who are interested in HCC.

Contents

• Foreword
• Preface
• List of Contributors
• 1. Cellular Origin of Hepatocellular Carcinoma
  Doris Schneller and Peter Angel.
  • INTRODUCTION
  • CELL OF ORIGIN OF HCC
  • LIVER CANCER STEM CELLS
  • THERAPEUTIC RESISTANCE OF LCSCS
  • CLINICAL IMPLICATIONS OF LCSCS
  • CONCLUSION
  • REFERENCES
• 2. The Role of the Tumor Microenvironment in the Development and Progression of Hepatocellular Carcinoma
  Ina Sevic, Fiorella Mercedes Spinelli, María José Cantero, Andrea Reszegi, Ilona Kovalszky, Mariana Gabriela García, and Laura Alaniz.
  • INTRODUCTION
  • THE TUMOR MICROENVIRONMENT
  • THE TUMOR MICROENVIRONMENT IN HCC DEVELOPMENT
  • THE TUMOR MICROENVIRONMENT IN HCC PROGRESSION AND METASTASIS
  • TARGETING THE MICROENVIRONMENT TO INHIBIT TUMOR GROWTH
  • CONCLUSION
  • REFERENCES
• 3. In Vitro Models of the Liver: Disease Modeling, Drug Discovery and Clinical Applications
  Scott D. Collins, Gloria Yuen, Thomas Tu, Magdalena A. Budzinska, Kevin Spring, Katherine Bryant, and Nicholas A. Shackel.
  • INTRODUCTION
  • IN VITRO LIVER MODELS
  • CONVENTIONAL 2D IN VITRO LIVER CELL CULTURES
  • 3D IN VITRO LIVER MODELS
  • FUTURE DIRECTIONS OF IN VITRO MODELS OF THE LIVER
  • CONCLUSION
  • REFERENCES
• 4. Mouse Models of Hepatocellular Carcinoma
  Rodrigo Carlessi, Julia Köhn-Gaone, John K. Olynyk, and Janina E. E. Tirnitz-Parker.
  • INTRODUCTION
  • CHEMOTOXIC MODELS
  • DIET-INDUCED MODELS
  • GENETICALLY ENGINEERED MODELS
  • CONCLUSION
  • REFERENCES
• 5. The Role of Lipids in Hepatocellular Carcinoma
  C. Nelson Hayes, Peiyi Zhang, and Kazuaki Chayama.
  • INTRODUCTION
  • NAFLD, CIRRHOSIS, AND HCC
  • HBV AND HCC
  • DE NOVO LIPOGENESIS IN HCC
  • LIPID METABOLIC REPROGRAMMING
  • LIPIDOMICS
  • THERAPEUTIC ADVANCES TARGETING LIPID METABOLISM
  • CONCLUSION
  • REFERENCES
• 6. Current Topics and Perspectives in Surgical Management of Hepatocellular Carcinoma
  Sebastian Lünse, Claus-Dieter Heidecke, and Lars Ivo Partecke.
  • INTRODUCTION
  • CURRENT SURGICAL MANAGEMENT OF HCC
  • PERSPECTIVES IN SURGICAL MANAGEMENT OF HCC
  • CONCLUSION
  • REFERENCES
• 7. Tyrosine Kinase Inhibitors in the Treatment of Hepatocellular Carcinoma
  Tiffany Sandra Wai Ling Khoo, Arif Rehman, and John K. Olynyk.
  • INTRODUCTION
  • SORAFENIB
  • LENVATINIB
  • REGORAFENIB
  • CABOZANTINIB
  • ADVERSE EFFECTS AND MANAGEMENT
  • CONCLUSION
  • REFERENCES
• 8. Multidrug Resistance in Hepatocellular Carcinoma
  Baojun Duan, Chen Huang, Jun Bai, Yu Lian Zhang, Xi Wang, Juan Yang, and Jun Li.
  • INTRODUCTION
  • MECHANISMS OF MDR
  • STRATEGIES TO OVERCOME MDR
  • CONCLUSION
  • REFERENCES

Hepatocellular Carcinoma

ISBN: 978-0-9944381-8-8

DOI: http://dx.doi.org/10.15586/hepatocellularcarcinoma.2019

Edited by

Janina E.E. Tirnitz-Parker, MSc, PhD, School of Pharmacy and Biomedical Sciences and Curtin Health Innovation Research Institute, Curtin University, Bentley, WA, Australia

Published by

Codon Publications

Brisbane, Australia

Copyright© 2019 Codon Publications

Copyright of individual chapters belongs to the respective authors. The authors grant unrestricted publishing and distribution rights to the publisher. The electronic versions of the chapters are published under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). https://creativecommons.org/licenses/by-nc/4.0/. Users are allowed to share and adapt the chapters for any non-commercial purposes as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source. The book in its entirety is subject to copyright by the publisher. The reproduction, modification, republication and display of the book in its entirety, in any form, by anyone, for commercial purposes are strictly prohibited without the written consent of the publisher.

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First Published in October 2019

Printed in Australia