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Cover
Title Page
Copyright
Dedication
Preface
1. 1 History of Cancer Signaling Research
2. 2 Outlook
3. 3 Intention of this Book
4. 4 Selection of Topics and Readers' Comments
5. 5 Structures of Chapters
6. 6 Figures and Video Animations
7. 7 Nomenclature and Abbreviations
Acknowledgments
List of Abbreviations
About the Companion Website
Chapter 1: General Aspects of Signal Transduction and Cancer Therapy
1. 1.1 General Principles of Signal Transduction
2. 1.2 Drugs against Cancer
3. 1.3 Outlook
4. References
Chapter 2: Tumor Cell Heterogeneity and Resistance to Targeted Therapy
1. 2.1 The Genetic Basis of Tumorigenesis
2. 2.2 Clonal Heterogeneity
3. 2.3 Tumor Stem Cells and Tumor Cell Hierarchies
4. 2.4 Epigenetics and Phenotypic Plasticity
5. 2.5 Microenvironment
6. 2.6 Outlook
7. References
Chapter 3: Cell Cycle of Tumor Cells
1. 3.1 Properties of Tumor Cells
2. 3.2 The Cell Cycle
3. 3.3 The Cell Cycle as Therapeutic Target
4. 3.4 Outlook
5. References
Chapter 4: Cell Aging and Cell Death
1. 4.1 A Cell's Journey through Life
2. 4.2 Cellular Aging and Senescence
3. 4.3 Cell Death
4. 4.4 Morphologies of Dying Cells
5. 4.5 Necroptosis
6. 4.6 Apoptosis in the Healthy Organism
7. 4.7 Apoptosis of Tumor Cells
8. 4.8 Autophagy
9. 4.9 Cell Death and Cell Aging as Therapeutic Targets in Cancer Treatment
10. 4.10 Senescence in Anticancer Therapy
11. 4.11 Outlook
12. References
Chapter 5: Growth Factors and Receptor Tyrosine Kinases
1. 5.1 Growth Factors
2. 5.2 Protein Kinases
3. 5.3 Therapy of Tumors with Dysregulated Growth Factors and their Receptors
4. 5.4 Outlook
5. References
Chapter 6: The Philadelphia Chromosome and BCR-ABL1
1. 6.1 Analysis of Chromosomes
2. 6.2 Aberrant Chromosomes in Tumor Cells
3. 6.3 The Philadelphia Chromosome
4. 6.4 The BCR-ABL1 Kinase Protein
5. 6.5 Outlook
6. References
Chapter 7: MAPK Signaling
1. 7.1 The RAS Gene
2. 7.2 The Ras Protein
3. 7.3 Neurofibromin: The Second RasGAP
4. 7.4 Downstream Signaling of Ras
5. 7.5 Therapy of Tumors with Constitutively Active MAPK Pathway
6. 7.6 Outlook
7. References
Chapter 8: PI3K-AKT-mTOR Signaling
1. 8.1 Discovery of the PI3K-AKT-mTOR Pathway
2. 8.2 Phosphatidylinositol-3-Kinase (PI3K)
3. 8.3 Inositol Trisphosphate, Diacylglycerol, and Protein Kinase C (PKC)
4. 8.4 AKT (Protein Kinase B)
5. 8.5 mTOR
6. 8.6 PTEN
7. 8.7 Activation of the PI3K/AKT/mTOR Pathway in Cancer
8. 8.8 PKC in Cancer
9. 8.9 Therapy
10. 8.10 Outlook
11. References
Chapter 9: Hypoxia-Inducible Factor (HIF)
1. 9.1 Responses of HIF to Hypoxia and Oncogenic Pathways
2. 9.2 HIF Functional Domains
3. 9.3 Regulation of HIF
4. 9.4 Regulation of HIF in Malignant Disease
5. 9.5 HIF Targets in Cancer
6. 9.6 TCA Cycle Intermediates and Tumor Syndromes
7. 9.7 Drugs Targeting HIFs
8. 9.8 Outlook
9. References
Chapter 10: NF-κB Pathways
1. 10.1 NF-κB Signaling in Inflammation, Growth Control, and Cancer
2. 10.2 The Core of NF-κB Signaling
3. 10.3 Family of IκB Proteins
4. 10.4 Canonical NF-κB Signaling from TNF Receptor 1
5. 10.5 B-Cell Receptor Signaling
6. 10.6 Other Receptors Activating the Canonical Pathway
7. 10.7 Alternative NF-κB Pathway
8. 10.8 Terminating the NF-κB Response
9. 10.9 Ubiquitinylation in NF-κB Signaling
10. 10.10 Transcriptional Regulation
11. 10.11 Physiological Role of NF-κB Transcription Factors
12. 10.12 Mutational Activation of NF-κB Pathways in Malignant Disease
13. 10.13 Cross Talk between Mutant KRas and NF-κB
14. 10.14 Inflammation, NF-κB, and Cancer
15. 10.15 Activation of Osteoclasts in Multiple Myeloma and Breast Cancer Metastases
16. 10.16 Targeting NF-κB Pathways
17. 10.17 Outlook
18. References
Chapter 11: Wnt Signaling
1. 11.1 The History of Wnt
2. 11.2 The Canonical Wnt Pathway
3. 11.3 The Wnt Network
4. 11.4 Proteins of the Wnt Pathway with Diverse Functions
5. 11.5 The Wnt Targetome
6. 11.6 The Wnt Pathway as Therapeutic Target
7. 11.7 Outlook
8. References
Chapter 12: Notch Signaling
1. 12.1 Introduction
2. 12.2 Determination of Cell Fate Decisions
3. 12.3 Notch Proteins and Notch Ligands
4. 12.4 Notch Signaling
5. 12.5 Notch Signaling in Malignant Disease
6. 12.6 Drugs Targeting the Notch Pathway
7. 12.7 Outlook
8. References
Chapter 13: Hedgehog Signaling
1. 13.1 Overview of Hedgehog Signaling
2. 13.2 Hedgehog Ligands
3. 13.3 The Primary Cilium
4. 13.4 Patched (Ptch) and Smoothened (Smo)
5. 13.5 Gli Transcription Factors
6. 13.6 Signaling in the Absence of Hedgehog
7. 13.7 Signaling after Binding of Hedgehog to Patched
8. 13.8 Activation of the Canonical Hedgehog Pathway in Basal Cell Carcinoma and Medulloblastoma
9. 13.9 Noncanonical Activation of Hedgehog-Responsive Genes
10. 13.10 Paracrine Activation of Hedgehog Signaling
11. 13.11 Pharmacological Inhibition of the Hedgehog Pathway
12. 13.12 Outlook
13. References
Chapter 14: TGFβ Signaling
1. 14.1 The TGFβ Superfamily
2. 14.2 Structure and Processing of TGFβ Superfamily Members
3. 14.3 The TGFβ Signaling Pathway
4. 14.4 Transcriptional Regulation by TGFβ Superfamily Members
5. 14.5 Regulation of Stem Cells by TGFβ Superfamily Members
6. 14.6 TGFβ Superfamily Members as Tumor Suppressors in Human Cancer
7. 14.7 Active role of TGFβ in Tumor Progression
8. 14.8 Drugs Interfering with TGFβ Signaling
9. 14.9 TGFβ Superfamily Members in Tumor Cachexia
10. 14.10 Outlook
11. Nomenclature
12. References
Index
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