Note: Front Cover -- Molecular and Cellular Changes in the Cancer Cell -- Copyright -- Contents -- Contributors -- Preface -- Part I: Overview: Genetic, Epigenetic and Cell Signaling Alterations -- Chapter One: Molecular and Cellular Changes During Cancer Progression Resulting From Genetic and Epigenetic Alterations -- 1. Introduction -- 1.1. Types of Chromatin -- 1.2. The Nucleosome and the Core Epigenetic Modifications -- 1.3. DNase Hypersensitivity Sites Are Linked With the Epigenomic Landscape -- 1.4. Depositing, Removing, and Interpreting Epigenetic Marks -- 2. DNA Methylation -- 2.1. Genome-Wide DNA Hypomethylation -- 2.2. Tumor Suppressor Gene Hypermethylation -- 2.3. CpG Island Methylator Phenotype -- 2.4. Viral Influences on Aberrant DNA Methylation -- 2.5. Therapeutic Reversal of Aberrant DNA Methylation -- 3. Lysine Acetylation -- 3.1. Acetyltransferases -- 3.2. Class I, II, and IV Deacetylases -- 3.3. Alterations in Class I, II, and IV Deacetylases in Human Tumors -- 3.4. Class I/II Deacetylase Inhibition -- 3.5. Sirtuins -- 3.6. Multiple SIRT1 Nonhistone Targets -- 3.7. Sirtuins in Cancer -- 3.8. Sirtuin Inhibition -- 4. Lysine and Arginine Methylation -- 4.1. Lysine Methyltransferases -- 4.2. Arginine Methyltransferases -- 4.3. Alterations in the MLL Lysine Methyltransferases in Human Tumors -- 4.4. Lysine Demethylases -- 4.5. Alterations in Lysine Demethylases in Human Tumors -- 5. Noncoding RNA -- 6. Epigenetic Readers -- 6.1. Readers of DNA Methylation -- 6.2. Readers of Lysine Acetylation and Methylation -- 7. Concluding Remarks -- References -- Chapter Two: Wnt/β Catenin-Mediated Signaling Commonly Altered in Colorectal Cancer -- 1. Wnt Signaling in Colorectal Cancer -- 1.1. Introduction to Wnt Signaling -- 1.2. Canonical Wnt Signaling and Colorectal Cancer -- 2. Mutations in the Wnt Signaling Pathway. , 2.1. Adenomatous Polyposis Coli -- 2.2. β-Catenin -- 2.3. Axin and Other Wnt Signaling Components -- 3. Cancer Stem Cells -- 3.1. Introduction to Cancer Stem Cells -- 3.2. Wnt: The Key Player in Cancer Cell Stemness -- 3.3. Cancer Stem Cell Markers -- 4. Treatments -- 4.1. Shortcomings of Current Treatment Regimes -- 4.2. ICG-001: Specific β-Catenin Inhibitor -- 4.3. Repurposed Drugs -- 4.4. Niclosamide: Antihelminth to Anticancer -- 4.5. Nitazoxanide: A Safer Relative of Niclosamide -- 4.6. Silibinin -- 4.7. Monensin -- 4.8. Other Wnt Inhibitors -- 5. Markers for Early Detection and Prognosis -- 5.1. Carcinoembryonic Antigen -- 5.2. APC and β-Catenin -- 5.3. S100A4 -- 5.4. Cancer Stem Cell Markers: CD133, CD44, ALDH1, and LGR5 -- 6. Summary -- References -- Chapter Three: Interplay Between Inflammation and Epigenetic Changes in Cancer -- 1. Introduction -- 2. Complex Relationship Between the Immune System and Cancer -- 2.1. Innate Immunity -- 2.2. Innate Immune Response in Tumors -- 2.3. Adaptive Immunity -- 2.4. Adaptive Immune Response in Tumors -- 3. Chronic Inflammatory Diseases Predispose Individuals to Cancer -- 3.1. H. pylori Infection and Gastric Cancer -- 3.2. Hepatitis C Virus (HCV) and Liver Cancer -- 3.3. Barrett´s Esophagus and Esophageal Cancer -- 3.4. IBD and Colorectal Cancer (CRC) -- 3.5. Ultraviolet (UV) Radiation and Skin Cancer -- 4. Overview of Epigenetics and Its Role in Normal Physiological Processes and Cancer -- 4.1. Overview of Epigenetics -- 4.1.1. Noncoding RNAs -- 4.1.2. Histone Modifications -- 4.1.3. DNA Methylation -- 4.2. Importance of Epigenetics in Embryonic Development -- 4.3. Importance of Epigenetics in Immune Cell Differentiation and Cytokine Expression -- 4.4. Epigenetic Alterations and Their Importance in Cancer Initiation and Progression. , 4.4.1. Silencing of Tumor Suppressor Genes and Activation of Oncogenes -- 4.4.2. Epigenetic Alterations That Allow Cancer Cells to Evade the Immune System -- 5. The Role of Inflammation in Initiating Epigenetic Alterations -- 5.1. Epidemiological Evidence Supporting a Connection Between Inflammation and Aberrant Epigenetic Alterations -- 5.2. In Vivo Studies Demonstrating a Relationship Between Inflammation and Epigenetic Alterations -- 5.3. In Vitro Studies Demonstrating a Relationship Between Inflammation and Epigenetic Alterations -- 5.4. Molecular Mechanisms Underlying Inflammation-Induced Epigenetic Alterations -- 5.4.1. Alteration of Cellular Metabolism and Epigenetic Protein Cofactors -- 5.4.2. The Role of DNA Damage in Inflammation-Induced Epigenetic Alterations -- 6. Cancer Prevention and Treatment -- 6.1. Antiinflammatory Agents -- 6.2. HDAC Inhibitors -- 6.3. Histone Lysine Demethylase Inhibitors -- 6.4. BET Inhibitors -- 6.5. Histone Lysine Methyltransferase Inhibitors -- 6.6. DNA Methyltransferase Inhibitors -- 6.7. Dietary Compounds -- 6.8. Immunotherapy -- 6.9. Combination Therapy -- 7. Concluding Remarks -- References -- Part II: Viral Influences in Cancer Initiation and Progression -- Chapter Four: Viral Carcinogenesis -- 1. RNA Retroviruses -- 1.1. History -- 1.2. Human T Cell Lymphotropic Virus 1 (HTLV-1) -- 1.3. Human Immunodeficiency Virus (HIV) -- 2. DNA Viruses -- 2.1. History -- 2.2. Simian Vacuolating Virus (SV40) -- 2.3. SV40 and Rb -- 2.4. SV40 and p53 -- 2.5. Human Papilloma Virus (HPV) -- 2.6. Human Polyoma Virus -- 2.7. Epstein-Barr Virus (EBV, HHV-4) -- 2.8. Kaposi´s Sarcoma-Associated Herpesvirus (KSHV, HHV-8) -- 2.9. Hepatitis B Virus (HBV) -- 3. RNA Viruses -- 3.1. Hepatitis C Virus (HCV) -- 4. Conclusion -- References -- Chapter Five: The Interaction Between Human Papillomaviruses and the Stromal Microenvironment. , 1. Introduction -- 2. The Stromal Microenvironment -- 3. The HPV Life Cycle -- 3.1. Two Caveats -- 4. Growth Factors -- 4.1. Transforming Growth Factor-Beta -- 4.1.1. Functions as a Growth Inhibitor and Activator -- 4.1.2. Interaction With HPV -- 4.2. Epidermal Growth Factor -- 4.2.1. EGFR Signaling -- 4.2.2. Relationship With HPV -- 4.3. Other Growth Factors -- 5. Fibroblasts -- 5.1. Fibroblasts as Epithelial Support Cells -- 5.2. Cancer-Associated Fibroblasts -- 5.3. Estrogen in the Stroma -- 6. Immune Interactions -- 6.1. Immunology of Stratified Epithelia -- 6.2. Innate Immune Responses Against HPV -- 6.2.1. TLRs and Nuclear Factor Kappa B -- 6.2.2. IFN Signaling -- 6.2.2.1. IFN and HPV -- 6.2.2.2. IFNκ -- 6.3. HPV Effects on Immune Cells -- 6.3.1. Langerhans Cells -- 6.3.1.1. Epithelial Recruitment -- 6.3.1.2. Differentiation and Maintenance -- 6.3.1.3. Maturation and Migration -- 6.3.1.4. LC Function -- 6.3.2. T Cells -- 6.3.2.1. HPV Interferes With Antigen Processing -- 6.3.2.2. T Cell Epitopes Are Poorly Immunogenic in the Context of Infection -- 6.3.2.3. HPV Skews the T Cell Response Away From Th1 -- 6.3.3. Other Cell Types -- 6.4. Soluble Immune Factors -- 6.4.1. Cytokines and Chemokines -- 6.4.2. Immune Functions of TGFβ -- 6.4.2.1. Innate Immunity -- 6.4.2.2. Cellular Immunity -- 6.4.2.3. TGFβ in Cervical Lesions -- 6.4.3. EGFR and the Immune Response -- 7. Angiogenesis and the Hypoxic Response -- 7.1. Angiogenesis in HPV Lesions -- 7.2. Regulation of Hypoxic Response and Angiogenesis by HPV -- 8. ECM and MMPs -- 9. Unresolved Questions -- References -- Part III: Pancreatic Cancer: Altered Signaling Networks and Emerging Treatment Strategies -- Chapter Six: Molecular Pathogenesis of Pancreatic Cancer -- 1. Introduction -- 2. Genetic Alterations in Pancreatic Cancer -- 2.1. Oncogenic KRAS Mutations -- 2.2. Tumor Suppressor Genes. , 2.3. TGF-β/SMAD4 Alterations -- 2.4. Telomere Abnormalities -- 3. Deregulated EMT in Pancreatic Cancer -- 4. Molecular Subtype Classifications of Pancreatic Cancer -- 5. Deregulated Signaling Networks in Pancreatic Cancer -- 5.1. The EGFR-KRAS Network -- 5.2. Hippo Signaling -- 5.3. Inflammation -- 5.4. Autophagy -- 6. Current and Future Therapeutic Strategies for Pancreatic Cancer -- 7. Conclusions -- References -- Chapter Seven: Current and Emerging Targeting Strategies for Treatment of Pancreatic Cancer -- 1. Introduction -- 2. Current Therapeutic Strategies -- 2.1. Surgery -- 2.2. Chemotherapy -- 2.3. Radiotherapy -- 3. Novel and Emerging Therapeutic Options -- 3.1. Immunotherapy-Based Approaches -- 3.1.1. Passive Immunotherapy -- 3.1.2. Active Immunotherapy -- 3.1.3. Immune Checkpoint Inhibitors -- 3.2. Chemoprevention and Neoadjuvant Strategies -- 3.2.1. Curcumin -- 3.2.2. Epiallocatechin-3-Gallate -- 3.2.3. Nonsteroidal Antiinflammatory Drugs -- 3.3. Hyaluronan and CD44 -- 3.4. Stromal Disruption -- 3.5. Epigenetics -- 3.5.1. DNA Methylation -- 3.5.2. Histone Modification -- 3.5.3. Histone Acetylation/Deacetylation -- 3.5.4. Histone Methylation -- 3.6. Noncoding RNAs -- 3.6.1. Long Noncoding RNA and PDAC -- 3.6.2. MicroRNAs and PDAC -- 3.6.3. Other Potential PDAC ncRNA Targets -- 3.7. PARP1 Inhibitors -- 4. Concluding Remarks -- References -- Part IV: Soft Tissue Sarcomas: Genomic and Epigenomic Alterations -- Chapter Eight: Molecular Changes Associated With Tumor Initiation and Progression of Soft Tissue Sarcomas: Targeting the ... -- 1. Introduction -- 2. Clinical Parameters of EWSR1-Translocation-Associated Soft Tissue Sarcoma Subtypes -- 2.1. Desmoplastic Small Round Cell Tumor (DSRCT) -- 2.2. Ewing´s Sarcoma (EWS) -- 2.3. Clear Cell Sarcoma of Soft Tissue (CCSST) -- 2.4. Extraskeletal Myxoid Chondrosarcoma (EMCS). , 2.5. Angiomatoid Fibrous Histiocytoma (AFH).