The Heterogeneity of Cancer Metabolism.

The Heterogeneity of Cancer Metabolism.

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Bibliographic Details
Superior document:Advances in Experimental Medicine and Biology Series ; v.1311
:
Le, Anne.
Place / Publishing House:Cham : : Springer International Publishing AG,, 2021.
©2021.
Year of Publication:2021
Edition:2nd ed.
Language:English
Series:Advances in Experimental Medicine and Biology Series
Online Access:
Physical Description:1 online resource (283 pages)
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Table of Contents:
  • Intro
  • Foreword
  • Preface
  • Acknowledgments
  • Contents
  • Editor and Contributors
  • About the Editor
  • Contributors
  • Part I: Basic Metabolism of Cancer Cells
  • Glucose Metabolism in Cancer: The Warburg Effect and Beyond
  • 1 Introduction
  • 2 The Warburg Effect
  • 2.1 Otto Warburg's Early Studies of Normal Cellular Respiration
  • 2.2 The Warburg Effect Is a Prominent Feature of Cancer Cell Metabolism
  • 2.3 The Biochemical Nature and Clinical Significance of the Warburg Effect
  • 2.4 Metabolic and Genetic Reprogramming Underlying the Warburg Effect
  • 3 Heterogeneity in Glucose Metabolism
  • 4 The Role of Glycogen Metabolism and Gluconeogenesis in Tumor Growth
  • 4.1 Glycogen Metabolism Is Upregulated in Several Cancers
  • 4.2 Upregulation of Gluconeogenic Enzymes in Cancer
  • 5 Success and Failures of Targeting Glucose Metabolism for Cancer Therapy
  • 5.1 Therapies Targeting Glycolysis and the Warburg Effect
  • 5.2 Therapies Targeting Glycogenolysis and Glycogen Synthesis Have Shown Promising Results
  • 6 Conclusion
  • References
  • Glutamine Metabolism in Cancer
  • 1 Introduction
  • 2 Characteristic Features of Glutamine Metabolism in Cancer
  • 2.1 Dysregulation of the TCA Cycle
  • 2.2 Glutamine Addiction
  • 2.3 The Metabolic Reprogramming of Cancers Provides Them with Alternative Sources of Glutamate: Via N-Acetyl-Aspartyl-Glutamate (NAAG) and via the Glutaminase II Pathway
  • 3 Targeting Glutamine Metabolism for Cancer Therapy
  • 3.1 Inhibition of Glutaminolysis by GLS Inhibitors
  • 3.2 Combination Therapy
  • 3.3 Knockdown of c-MYC
  • 3.4 Inhibition of Glutamate Dehydrogenase (GDH)
  • 3.5 Inhibiting the TCA Cycle by Depleting Glutamine, α-Ketoglutarate, and Asparagine
  • 3.6 Inhibiting Glutamine Uptake
  • 3.7 Using Glutamine Mimetics.
  • 4 Transaminase Upregulation and Targeting Amino Acid Synthesis for Cancer Therapy
  • 5 Glutamine Metabolism in the Tumor Microenvironment
  • 5.1 The Role of Glutamine Metabolism in T Cells and NK Cells
  • 5.2 The Role of Glutamine Metabolism in Tumor-Associated Macrophages
  • 5.3 The Role of Glutamine Metabolism in Cancer-Associated Fibroblasts
  • 6 Conclusion
  • References
  • The Heterogeneity of Lipid Metabolism in Cancer
  • 1 Introduction
  • 2 Fatty Acid Synthesis Is Upregulated in Cancer
  • 2.1 The Mitochondrial Citrate Transporter Protein (CTP) Protects Mitochondrial Function in Cancer
  • 2.2 ATP Citrate Lyase (ACLY) Is Upregulated in Cancer
  • 2.3 Multifaceted Effects of Inhibiting Acetyl-CoA Carboxylase (ACC) in Cancer
  • 2.4 The First Fatty Acid Synthase (FAS) Inhibitor TVB-2640 Is in Clinical Trials for Cancer
  • 2.5 Which Markers Can Predict Cancer Cell Sensitivity to Lipid Synthesis Inhibition?
  • 2.6 Tumor Microenvironment Influences the Sensitivity of Cancer Cells to Lipid Synthesis Inhibitors
  • 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
  • 6.1 Targeting FAO for Cancer Therapy May Be Achieved by Inhibiting Carnitine Palmitoyltransferase 1
  • 6.2 CPT1 Inhibitors Are Now in Clinical Trials
  • 6.3 FAO for Very-Long-Chain Fatty Acids Occurs at the Peroxisome Where Peroxisome Proliferator-Activated Receptors (PPARs) Act as Ligand-Activated Transcription Factors
  • 7 Conclusion
  • References
  • Part II: Heterogeneity of Cancer Metabolism
  • The Multifaceted Glioblastoma: From Genomic Alterations to Metabolic Adaptations
  • 1 Introduction
  • 2 GBM Classifications and Intratumoral Heterogeneity.
  • 2.1 GBM Subtype Classification
  • 2.2 Intratumoral Heterogeneity
  • 2.2.1 Liquid Biopsy as a Method for Detecting Heterogeneity and Longitudinal Tracking
  • 2.2.2 Glioblastoma Stem Cell Resistance and Recurrence Are Supported Through Mitochondrial Activity and Fatty Acid Oxidation
  • 3 Genomic Alterations Lead to Distinct Metabolic Changes Allowing for Targeted Therapies
  • 3.1 PTEN Mutations Lead to High Rates of Glycolysis, Facilitating Survival in Harsh Microenvironments
  • 3.2 EGFR Mutations Shift Cancer Cells toward a Glycolytic Phenotype and Permit Survival under Glucose-Deprived Conditions
  • 3.3 p53 Mutations Result in Activation of the Warburg Effect
  • 3.4 GBM Exhibits Upregulated Glutamine Metabolism Allowing for Targeted Vulnerabilities Through GLS, GS, and mTOR
  • 3.5 Lipid Metabolism Dysregulation Following BRAF Mutations and EGFR Signaling Provides Clues for New GBM Therapeutic Strategies
  • 3.6 GBMs Rely on the TCA Cycle and Its Reductants
  • 3.7 IDH1 Mutations Lead to Oncometabolite Production and Glutamine Addiction and Act as a Prognostic Marker
  • 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
  • 1 Introduction
  • 2 Oncogenic KRAS Regulates Metabolism in Pancreatic Cancer Cells (Fig. 2)
  • 2.1 Oncogenic KRAS Regulates Glutamine Metabolism
  • 2.2 Oncogenic KRAS Regulates Glucose Metabolism
  • 2.3 Oncogenic KRAS Upregulates Macropinocytosis and Lipid Scavenging
  • 3 Other Alternative Metabolisms in Pancreatic Cancer
  • 3.1 MUC1 Overexpression Leads to Increased Glucose Metabolism
  • 3.2 p53 Functions Predict the Sensitivity of Pancreatic Cancer Tumors to Glycolytic Inhibition
  • 3.3 Alternative Source of Glutamate in PDAC.
  • 3.3.1 Neurotransmitter N-Acetyl-Aspartyl-Glutamate (NAAG) as a Glutamate Reservoir in Cancer
  • 3.3.2 Glutaminase II Pathway Is Another Source of Glutamate in Cancer
  • 4 Pancreatic Tumor Microenvironment
  • 4.1 PDACs are Dependent on Autophagy
  • 4.2 Stromal Interactions Create Complex PDAC Metabolic Networks
  • 5 Suggested Therapy (Fig. 3)
  • 5.1 Targeting Alpha-Ketoglutarate Dehydrogenase Complex Function by CPI-613 to Slow Mitochondrial Metabolism
  • 5.2 Antidiabetic Drug, Metformin, Targets Pancreatic Cancer Stem Cells
  • 5.3 Combined Therapy to Target Pancreatic Metabolism Heterogeneity
  • 5.4 Targeting PDACs Based on Metabolic Subtype within the PDAC Tumor Microenvironment
  • 5.5 Autophagy Inhibition via Hydroxychloroquine
  • 6 Conclusion
  • References
  • The Heterogeneity of Breast Cancer Metabolism
  • 1 Introduction
  • 2 Aberrant Metabolic Pathways Present in Breast Cancer Contribute to Breast Cancer Heterogeneity (Fig. 1)
  • 2.1 Differences in Glycolytic Upregulation Among Breast Cancer Subtypes Can Be Attributed to Glucose Transporter (GLUT) Expression
  • 2.2 Choline Metabolism in Breast Cancer Is Strongly Associated with Tumor Grades
  • 3 Different Roles of Estrogen in Estrogen Metabolism and ER Binding Promote Breast Cancer Tumorigenicity
  • 3.1 PHGDH Overexpression in Serine Biosynthesis Fuels TCA Anaplerosis
  • 4 The Clinical Applications of Metabolic Profiling
  • 4.1 Breast Cancer Diagnosis and Subtyping Using Metabolomics
  • 4.2 Metabolic Profiling as a Strategy for Prediction of Recurrence in Breast Cancer
  • 4.3 Metabolic Fingerprinting in Breast Cancer Metastasis
  • 4.4 Prediction of Response to Therapy Based on Metabolic Phenotypes
  • 5 Additional Perspectives on Breast Cancer Heterogeneity
  • 5.1 Spatial Pathogenesis Observed in Breast Cancer Metabolism.
  • 5.2 Temporal Pathogenesis Observed in Breast Cancer Metabolism: Metabolic Differences Between Early Stage and Advanced Stage
  • 5.3 Metabolic Heterogeneity Influences Effective Breast Cancer Drug Treatment
  • 6 Conclusion
  • References
  • Non-Hodgkin Lymphoma Metabolism
  • 1 Introduction
  • 2 Lymphoma Metabolism Exhibits Multifaceted Characteristic Features Which Are Correlated to Poor Prognosis
  • 2.1 Aggressive Lymphomas Exhibit the Warburg Effect
  • 2.2 Lactic Acidosis Is a Result of Overproduction of Lactate and Leads to a Fatal Prognosis
  • 3 Genetic Alterations Lead to Different Metabolic Phenotypes in NHL (Fig. 2)
  • 3.1 Mutation of p53 Helps Cancer Cells Survive Glutamine Deprivation
  • 3.2 PI3K Regulates Fatty Acid Synthesis (FAS) in Primary Effusion Lymphoma (PEL) and Other B-NHLs
  • 3.3 AMPK Regulates NADPH Balance for Fatty Acid Oxidation (FAO) as a Means of Supplementing the Tricarboxylic Acid (TCA) Cycle
  • 3.4 PRPS2 Couples Protein and Nucleotide Biosynthesis to Drive Lymphomagenesis
  • 3.5 mTOR Activation Promotes Fatty Acid Synthesis (FAS)
  • 3.6 MYC Regulates Cancer Cell Metabolism under Glucose-Deprived and Hypoxic Conditions
  • 3.7 HIF-1 Acts as a Regulator in Hypoxia Adaptation and the Related Metabolic Changes
  • 3.8 Understanding the PI3K/AKT/mTOR Pathway in Lymphoma Can Lead to a Variety of Treatments
  • 4 Metabolic Profiling for Monitoring Tumor Progression and Guiding Treatment
  • 4.1 [18F]FDG PET/CT
  • 4.2 Systemic NAAG Concentrations for Tumor Growth Monitoring
  • 5 Conclusion
  • References
  • The Heterogeneity Metabolism of Renal Cell Carcinomas
  • 1 Introduction
  • 2 Different Oncogenic Mutations Lead to Different Metabolic Phenotypes in RCC (Fig. 1)
  • 2.1 Loss of the von Hippel-Lindau Tumor-Suppressor Gene Results in Metabolic Alterations Including Shifts Toward Aerobic Glycolysis in RCC.
  • 2.2 Fumarate Hydratase Mutations Result in an Increase in Aerobic Glycolysis in RCC.

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