Contents

• Foreword
• Preface
• Acknowledgments
• Editor and Contributors
• I. Basic Metabolism of Cancer Cells
  • Glucose Metabolism in Cancer: The Warburg Effect and Beyond
    Sminu Bose, Cissy Zhang, and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. The Warburg Effect
    • 3. Heterogeneity in Glucose Metabolism
    • 4. The Role of Glycogen Metabolism and Gluconeogenesis in Tumor Growth
    • 5. Success and Failures of Targeting Glucose Metabolism for Cancer Therapy
    • 6. Conclusion
    • References
  • Glutamine Metabolism in Cancer
    Ting Li, Christopher Copeland, and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Characteristic Features of Glutamine Metabolism in Cancer
    • 3. Targeting Glutamine Metabolism for Cancer Therapy
    • 4. Transaminase Upregulation and Targeting Amino Acid Synthesis for Cancer Therapy
    • 5. Glutamine Metabolism in the Tumor Microenvironment
    • 6. Conclusion
    • References
  • The Heterogeneity of Lipid Metabolism in Cancer
    Joshua K. Park, Nathan J. Coffey, Aaron Limoges, and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Fatty Acid Synthesis Is Upregulated in Cancer
    • 3. Targeting Fatty Acid Elongation
    • 4. The Efficacy of Inhibiting Cholesterol Synthesis with Adjuvant Statins Is Variable
    • 5. Fatty Acid Uptake Is Associated with Metastasis
    • 6. Fatty Acid Oxidation Encompasses a Diverse Set of Molecular Mechanisms
    • 7. Conclusion
    • Acknowledgments
    • References
• II. Heterogeneity of Cancer Metabolism
  • The Multifaceted Glioblastoma: From Genomic Alterations to Metabolic Adaptations
    Addison Quinones and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. GBM Classifications and Intratumoral Heterogeneity
    • 3. Genomic Alterations Lead to Distinct Metabolic Changes Allowing for Targeted Therapies
    • 4. Benefits of Combined Therapy
    • 5. Advanced Brain Tumors (GBM) Display Distinct Metabolic Profiles Compared to Lower Grade Tumors
    • 6. Conclusion
    • References
  • The Intricate Metabolism of Pancreatic Cancers
    Felipe Camelo and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Oncogenic KRAS Regulates Metabolism in Pancreatic Cancer Cells (Fig. 2)
    • 3. Other Alternative Metabolisms in Pancreatic Cancer
    • 4. Pancreatic Tumor Microenvironment
    • 5. Suggested Therapy (Fig. 3)
    • 6. Conclusion
    • References
  • The Heterogeneity of Breast Cancer Metabolism
    Jessica Tan and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Aberrant Metabolic Pathways Present in Breast Cancer Contribute to Breast Cancer Heterogeneity (Fig. 1)
    • 3. Different Roles of Estrogen in Estrogen Metabolism and ER Binding Promote Breast Cancer Tumorigenicity
    • 4. The Clinical Applications of Metabolic Profiling
    • 5. Additional Perspectives on Breast Cancer Heterogeneity
    • 6. Conclusion
    • References
  • Non-Hodgkin Lymphoma Metabolism
    Brian James Kirsch, Shu-Jyuan Chang, Michael James Betenbaugh, and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Lymphoma Metabolism Exhibits Multifaceted Characteristic Features Which Are Correlated to Poor Prognosis
    • 3. Genetic Alterations Lead to Different Metabolic Phenotypes in NHL (Fig. 2)
    • 4. Metabolic Profiling for Monitoring Tumor Progression and Guiding Treatment
    • 5. Conclusion
    • References
  • The Heterogeneity Metabolism of Renal Cell Carcinomas
    Mohammadreza Zarisfi, Tu Nguyen, Jessie R. Nedrow, and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Different Oncogenic Mutations Lead to Different Metabolic Phenotypes in RCC (Fig. 1)
    • 3. Metabolic Signatures of RCC
    • 4. RCC Therapy
    • 5. Conclusion
    • References
  • The Heterogeneity of Liver Cancer Metabolism
    Javier Salazar and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Different Oncogenic Mutations Lead to Different Metabolic Phenotypes in Primary Liver Cancer
    • 3. Metabolic Differences Between Liver Cancer Stem Cells (LCSCs) and Non-liver Cancer Stem Cells (Non-LCSCs)
    • 4. Metabolic Signatures of Liver Cancer
    • 5. New Therapeutic Investigations Based on Metabolism Studies
    • 6. Conclusion
    • References
  • Different Tumor Microenvironments Lead to Different Metabolic Phenotypes
    Marjorie Justine Antonio, Cissy Zhang, and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. The Tumor Microenvironment
    • 3. Different Tumor Microenvironments (TMEs) Lead to Different Metabolic Phenotypes
    • 4. Nutrient Utilization Can Predict a Tumor’s Metabolic Dependencies In Vivo
    • 5. Distinct, and Often Complementary, Metabolic Processes Operate Concurrently Within a Single Tumor
    • 6. Conclusion
    • References
  • The Intratumoral Heterogeneity of Cancer Metabolism
    Karim Nabi and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Multiple Theories Explain Cancer’s Heterogeneous Nature
    • 3. Intratumoral Metabolic Heterogeneity Follows Intratumoral Genetic Alterations
    • 4. Epigenetics Alterations Lead to Intratumoral Metabolic Heterogeneity
    • 5. Intratumoral Metabolic Adaptation and Heterogeneity Are Due to the Intemperate Conditions of the Tumor Microenvironment
    • 6. Metabolic Heterogeneity Leads to Unpredictable Outcomes
    • 7. Tailored Clinical Applications and Therapies Targeting Metabolic Pathways Can Lead to Better Clinical Outcomes
    • 8. Conclusion
    • References
  • Cancer Stem Cell Metabolism
    Fidelia B. Alvina, Arvin M. Gouw, and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. High Levels of Glycolytic Enzymes and Activities in CSCs (Fig. 2)
    • 3. Effects of Deregulation of Glutamine Metabolism on CSCs (Fig. 2)
    • 4. Mitochondrial Metabolism (Fig. 3)
    • 5. Lipid Metabolism (Fig. 4)
    • 6. Conclusion
    • References
  • Metabolism of Immune Cells in the Tumor Microenvironment
    Jin G. Jung and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Tumor Immunity and the Various Roles of Immune Cells
    • 3. Targeting the Metabolism of Immune Cells for Cancer Treatment
    • 4. Conclusion
    • References
• III. Relationship Between Cancer Cells and Cancer-Associated Fibroblasts
  • Metabolic Relationship Between Cancer-Associated Fibroblasts and Cancer Cells
    Christos Sazeides and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. CAFs Undergo the Reverse Warburg Effect and Provide Cancer Cells with Glycolytic Metabolites
    • 3. The Interaction Between Cancer Cells and CAFs Helps Cancer Cells Manage the Warburg Effect
    • 4. Loss of Stromal Cav-1 Is an Indicator of Poor Prognosis in Breast Cancers
    • 5. miRNAs Play a Crucial Role in CAF Metabolic Reprogramming
    • 6. CAF-Derived Exosomes (CDEs) Can Reprogram the Metabolic Pathway of Cancer Cells
    • 7. CAF-Derived Lactate Is more Than Just a Metabolite
    • 8. CAFs “Surrender” Their Functional Mitochondria to Prostate Cancer Cells
    • 9. CAFs Augment Cancer Addiction to Glutamine and Its Metabolically Relevant Consequences
    • 10. Alanine Secreted by Pancreatic Stellate Cells Supports Pancreatic Cancer Metabolism
    • 11. CAFs Act as Lipid Synthesis Factories for Colorectal Cancer Cells
    • 12. Reciprocal Communication Is Essential for Cancer Progression
    • 13. Conclusion
    • References
  • Targeting Metabolic Cross Talk Between Cancer Cells and Cancer-Associated Fibroblasts
    Jin G. Jung and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Overview of the Metabolism of CAFs in Solid Tumors
    • 3. Targeting the Metabolic Exchanges Between CAFs and Cancer Cells
    • 4. Targeting the Glutamine Uptake of Cancer Cells from CAFs
    • 5. Targeting Ketone Bodies and Ketosis in CAFs
    • 6. Targeting Fatty Acid, a Nutrient Reservoir for Cancer Cell Growth, from Cancer-Associated Adipocytes (CAAs)
    • 7. Conclusion
    • References
• IV. The Metabolic Interplay Between Cancer and Other Diseases
  • Diabetes and Cancer: The Epidemiological and Metabolic Associations
    Cissy Zhang and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. The Epidemiological Association: Diabetes Correlates with Increased Risk for Many Types of Cancer
    • 3. Abnormal Glucose Metabolism Serves as a Link Between Diabetes and Cancer
    • 4. Obesity Leads to Insulin Resistance in Diabetes and Oxidative Stress, Which Can Lead to Cancer (Fig. 1)
    • 5. Amino Acid Metabolism Plays Important Roles in Both T2D and Cancer
    • 6. Exploiting the Similarities and Relationships Between Diabetes and Cancer Metabolism for Cancer Treatment (Fig. 2)
    • 7. Conclusion
    • References
  • Bridging the Metabolic Parallels Between Neurological Diseases and Cancer
    Shenghao Guo, Yanni Gu, Jiayin Qu, and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Glutamine Plays a Vital Role in Both Cancer Growth and Neurological Diseases
    • 3. GABA and Its Multiple Functions in Neurological Diseases and Cancer
    • 4. NAAG and Its Versatile Role in Neurological Diseases and Cancer
    • 5. Conclusion
    • References
  • Metabolic Intersection of Cancer and Cardiovascular Diseases: Opportunities for Cancer Therapy
    Giang Hoang, Kiet Nguyen, and Anne Le.
    Published online: May 21, 2021.
    • Key Points
    • 1. Introduction
    • 2. Glutamine Metabolism as a Prognostic and Therapeutic Target in Cancer and Cardiovascular Diseases (Fig. 1)
    • 3. Lipid Metabolism Plays an Important Role in Cancer Proliferation and Cardiovascular Disease Progression (Fig. 2)
    • 4. Upregulated Tryptophan Catabolism Has Been Linked to the Progression of Cardiovascular Diseases and Enhanced Immune System Evasion in Cancer (Fig. 3)
    • 5. Pyruvate Metabolism Abnormality Is Associated with Cardiovascular Diseases and Chemoresistance in Cancer
    • 6. Conclusion
    • References

This book is dedicated to my colleague and mentor, Dr. Arthur J. L. Cooper.