Molecular Targets and Cancer Therapeutics (Part 1)

Today, treatment options for cancer patients typically include surgery, radiation therapy, immunotherapy, and chemotherapy. While these therapies have saved lives and reduced pain and suffering, cancer still takes millions of lives every year around the world. Researchers are now developing advanced therapeutic strategies such as immunotherapy, targeted therapy, and combination nanotechnology for drug delivery. In addition, the identification of new biomarkers will potentiate early-stage diagnosis. Molecular Targets and Cancer presents information about cancer diagnosis and therapy in a simple way. It covers several aspects of the topic with updated information on par with medical board levels. The book features contributions from experts and includes an overview of cancer from basic biology and pathology, classifications, surveillance, prevention, diagnosis, types of cancer, treatment and prognosis. The first part of this book introduces the reader to cancer epidemiology, genetic alterations in cancer, exogenous and endogenous factors in carcinogenesis, roles for growth factors in cancer progression, cell signaling in cancer, transcription factors in cancer, and cancer genetics and epigenetics. This comprehensive guide is a valuable resource for oncologists, researchers, and all medical professionals who work in cancer care and research. Cover Title Copyright End User License Agreement Contents Preface Dedication List of Contributors Introduction Abdulaziz Bin Saeedan1,*, Mohd. Nazam Ansari1 and Amal Almohisen2 INTRODUCTION Definition Characteristics of Cancer The Hallmarks of Cancer Features of Cancer Cell Epidemiology of Cancer Cancer Epidemiology in the World Cancer Epidemiology in the Kingdom of Saudi Arabia Cancer Registries CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Cancer Traits; Present and Future Khalid A. Asseri1,* and Afaf Ahmed Aldahish2 INTRODUCTION Mechanisms of Contact Inhibition and its Evasion MALIGNANCY SUPPORTED BY THE DEFECTS OF THE TGF-Β PATHWAY TUMOR CELL SURVIVAL AND DEATH MEDIATES AUTOPHAGY Tumorigenesis and Tumor Progression Autophagy Autophagy Inhibits Tumor Progression NECROSIS HAS PRO-INFLAMMATORY AND TUMOR-PROMOTING POTENTIAL NECROPTOSIS: A PRO- OR ANTI-INFLAMMATORY MODE OF CELL DEATH NEW FUNCTION OF TELOMERASE Tumorigenesis Due to Malfunction of Telomere Telomeres as Suppressors of Tumors Telomeresas a Potential Target for Therapy THE NEXT GENERATION OF INDUCING ANGIOGENESIS Vascular Endothelial Growth Factor (VEGF) Role in Angiogenesis Cancer Therapy and HIF-1 Inhibitors THE NEXT GENERATION OF ACTIVATING INVASION AND METASTASIS Invasion and Migration Epithelial-to-Mesenchymal Transition (EMT) and Metastasis The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells Cancer Cells Promote their Own Growth Abnormalities in the Cell Cycle Control Proteins in Cancer CDK and CDK Activating Enzyme CKI Cell Cycle Control and Cancer Treatment CANCER OPPOSE APOPTOSIS The Extrinsic Pathway The Intrinsic Pathway The Final Pathway: Caspases INHIBITORY SIGNALS THAT MAY GENERALLY STOP CANCER DEVELOPMENT Immune Checkpoint Inhibitors PD-1 Inhibitors CTLA-4 Inhibitors CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENT REFERENCES Exogenous Factors and Cancer Baraa T. Alhajhussein1,*, Majed H. Wakid2, Najwa Mohamad Alsawi3, Hesham Hamdy Amin3,4 and Fahad Nasser Alonazi5 INTRODUCTION BACTERIA AND CANCER Direct Bacterial Carcinogenesis Indirect Bacterial Carcinogenesis Other Roles for Bacteria in Cancer Bacterial Cancer Therapy PARASITES AND CANCER Blood Flukes Mechanism Liver Flukes Mechanism Indirect Carcinogenic Parasites VIRAL ONCOGENESIS Epstein-Barr Virus (EBV) Human Papillomaviruses (HPVs) Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Human Immunodeficiency Virus Human Herpes Virus 8 (HHV-8) Human T-Lymphotropic Virus-1 (HTLV-1) Merkel Cell Polyomavirus (MCV) How Viruses Cause Cancer? ROLE OF FREE RADICALS, CHEMICALS IN ONCOGENESIS Sources of Free Radicals Environmental Carcinogens as a Source of Free Radical Development of Cancer and Free Radicals Initial Stage of Tumor Formation and Free Radicals Proliferation of Tumor Cells and Free Radicals Angiogenesis and Free Radicals Metastasis and Free Radicals PHYSICAL ONCOGENIC FACTORS CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Biology of Cancer Rawiah A. Alsiary1,*, Hanadi A. Katouah2, Hiba S. Al-Amodi3 and Mashael Al-Toub4 INTRODUCTION CANCER CELLS AND CANCER STEM CELLS INTRODUCTION Cancer and Tumor Cancer Cells Cancer Stem Cells ENDOTHELIAL CELLS INTRODUCTION Angiosarcomas Tumor Endothelial Cells (TECs) Tumor Endothelial Markers (TEMs) Metastasis Cancer Regulatory Systems Angiogenesis PERICYTES INTRODUCTION PCs Origins and Activation PCs Contribution to Tumor Microenvironment and Cross-Talk with Cancer Cells IMMUNE INFLAMMATORY CELLS INTRODUCTION TAMs B Lymphocytes T Lymphocytes Infiltrating Cells Tumor-Infiltrating Lymphocytes (TILs) Myeloid-Derived Suppressor Cells (MDSCs) CANCER-ASSOCIATED FIBROBLAST (CAF) INTRODUCTION CAFs Origins and Activation CAFs Contribution to the Tumor Microenvironment and Cross-Talk with Cancer Cells TUMOR MICROENVIRONMENT (TME) INTRODUCTION Cancer-Non-Cancer Cell Interactions Mechanism Heat Shock Proteins (HSPs) Tumor Microenvironment Alterations at the Histological Level During Carcinogenesis TME at the Early Human Carcinogenesis Stage TME at the Advanced Human Carcinogenesis Stage CONCLUSION GENOMIC INSTABILITY AND MUTATION INTRODUCTION Cell Cycle Regulation of the Cell Cycle Genomic Instability Levels Nucleotide Instability (NIN) Microsatellite Instability (MSI) Chromosomal Instability (CIN) Checkpoints of DNA Damage Mitotic Checkpoints Telomere Maintenance DNA Repair Pathways Conclusion Remarks TUMOR-PROMOTING INFLAMMATION INTRODUCTION “Normal” Inflammation & Inflammatory Response in Tumor and General Mechanisms Inflammation & Tumor Initiation and Progression Involvement of Inflammatory Mediators in Genetic Mutations; Paving the Way for Carcinogenesis CONCLUSION REPROGRAMMING ENERGY METABOLISM INTRODUCTION Glycolysis Krebs Cycle Hexose Monophosphate Shunt (HMS) Lipid Metabolism Amino Acid Metabolism Mitochondria and its Central Role in Carcinogenesis Metabolic Alteration by p53 Metabolic Alteration by Kras Concluding Remarks CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Growth Factors and Cancer Aisha Al Anazi1,*, Ravi Teja Chitturi Suryaprakash2, Kate Shearston2 and Omar Kujan2 GROWTH FACTOR INDUCED BASEMENT MEMBRANE BREAKDOWN AND INVASION IN CANCER Growth Factor-Induced Basement Membrane Breakdown and Invasive Growth Intravasation Role of Breaching of the Basement Membrane in Tumour Progression The Transforming Growth Factor-β Induced Invasion TGF-β-Induced Epithelial to Mesenchymal Transformation Epigenetic Modification and Basement Membrane Invasion CURRENT UNDERSTANDING OF THE ROLE OF INTRAVASATION, EXTRAVASATION AND DISSEMINATION IN THE DEVELOPMENT OF CANCER Intravasation Macrophage-Assisted Tumour Cell Intravasation Intravasation of Tumour Cells Fusing with Macrophages Intravasation Associated with Trogocytosis Extravasation Tumor Cell Properties Promoting Extravasation Therapeutic Targets: Intravasation and Extravasation Extravasation of Leukocytes and Tumour Cells Dissemination Dissemination of Cancer Cells from a Primary Tumour GROWTH FACTORS INDUCE EVASION FROM CYTOTOXIC THERAPIES: AS TARGETS FOR A NEW STRATEGY IN CANCER TREATMENT Cytotoxic Therapy: An Alternative Approach to Treat Cancer Cells Growth Factor-Mediated Evasion from Cytotoxicity T-Cell-Mediated Cytotoxicity TGF-β and its Role in Tumour Evasion of Immune Surveillance GROWTH FACTORS INDUCE ANGIOGENESIS Mechanism of Angiogenesis in Cancer Vascular Endothelial Growth Factor (VEGF) Fibroblast Growth Factor (FGF) Other Modes of Tumour Vascularization GROWTH FACTORS INVOLVED IN TUMOUR PROGRESSION Platelet-Derived Growth Factor (PDGF) Family Vascular Endothelial Growth Factor (VEGF) Family Neuregulins and the EGF Family Epidermal Growth Factor (EGF) Fibroblast Growth Factor (FGF) Family Hepatocyte Growth Factor (HGF) Transforming Growth Factor-β (TGF-β) Insulin-Like Growth Factor (IGF) Family Neurotrophin Family (NF) CANCER THERAPEUTICS TARGETING GROWTH FACTOR SIGNALING Drugs and Mab that Target Receptors Targeting of VEGF Signalling Pathways Targeting TGF-β Signaling Tyrosine Kinase Inhibitors Ligand Traps of Growth Factors Oligonucleotide-Based Therapeutics CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Cell Signaling Pathways in Cancer Hajir A. Al-Saihati1,*, Mashael Al-Toub2, Hanaa I. Sharaf3, Manjari Singh4, Mohd. Nazam Ansari5 and Abdulaziz Bin Saeedan5 INTRODUCTION JAK/STAT Signaling Pathway General Features of the JAK/STAT Pathway The Role of the JAK/STAT Pathway in Cancer Notch Signaling Pathway General Features of the Notch Signaling Pathway The Role of the Notch Signaling Pathway in Cancer MAP Kinase, ERK, Ras, and Raf Pathways General Features of the Map Pathway General Features of the ERK Pathway General Features of Ras Signaling Pathway Raf Regulation PI3/AKT Signaling Pathway General Features of the PI3/AKT Signaling Pathway The Role of the PI3/AKT Signaling Pathway in Cancer Association Between PI3/AKT and Different Types of Cancer Treatment for the PI3K/AKT Signaling Pathway Nuclear Factor Kappa B (NFκB) Signaling Pathway General Features of the NFκB Signaling Pathway The Role of the NFκB Signaling Pathway in Cancer The Role of the NFκB Signaling Pathway in Cancer Therapy Wnt/β-Catenin Signaling Pathway General Features of the Wnt/β-Catenin Signaling Pathway The Role of the Wnt/β-Catenin Pathway in Cancer TGF-β General Features of TGF-β Role of TGF-β in Carcinogenesis CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Transcription Factors in Cancer Rawiah A. Alsiary1,*, Talat Abdullah Albukhari2 and Waheed A. Filimban3 TRANSCRIPTION FACTORS IN CANCER Signal Transducer and Activator of Transcription (STAT) Definition Types of STATs Features of the STAT Group of Proteins Biochemical Cascade Modes of STAT Activation The Standard Janus Kinase (JAK)-STAT Path Transcriptional Engagement Activation and Functions of STAT Proteins Inactivation of STAT Proteins Mutations Affecting STAT Signaling Cancer & STAT Family Protein STAT Proteins as Targets for Treatment STAT Engagement in Immunotherapy Therapeutic Techniques of Targeting STATS Summary Nuclear Factor-Κb (Nf-Κb) Tumor Transcription Factor Definition of NF-κB NF-κB Subunits NF-κB Signalling Pathway Canonical Pathway Non-Canonical Pathway Role of NF-κB in Cancer Mechanisms Implicated in Tumor Generation NF-κB (Transcription Factor in Tumors) NF-κB as a Transcription Factor NF-κB in Brain Tumors NF-κB Inhibition using Chemical Compounds Activating Mutations of NF-κB Pathway NF-kB and Activin-Induced Colorectal Cancer Migration NF-κB Hyperactivation and Esophageal Squamous Cell Carcinoma Summary WNT (Β)-CATENIN SIGNALING Introduction Wnt (β)-Catenin Signalingprotein Wnt/β-Catenin Signalling Receptor: Frizzled and LRP5/6 Wnt/β-Catenin Signaling Modulators Wnt Signalling Functions in Cancer Progression NOTCH AND HEDGEHOG SIGNALLING PATHWAYS Introduction Notch Signalling Pathway The Components and Process of Notch Signalling Pathways The Hedgehog Signalling Pathway The Components and Process of Hedgehog Signalling Pathway CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Epigenetic and Genetics Factors Abeer A. Alsofyani1,* and Yazan Samih Said2 MOLECULAR MACHINERY FOR METHYLATING DNA MOLECULAR MACHINERY FOR HISTONE MODIFICATION Acetylation of Lysine Methylation of Histone Methylation of Lysine Methylation of Arginine Arginine/Lysine Histone Demethylation Histone Phosphorylation Other Modifications Mechanism of Histone Modifications Direct Structural Perturbation Regulating the Binding of Chromatin Factor Histone Modification Communications CHROMATIN REMODELING COMPLEXES Remodeler Families MICRORNAS AN ANALYSIS OF EPIGENETIC GENE SILENCING IN CANCER Aberrant DNA Methylation in Cancer DNA Hypomethylation DNA Hypermethylation Aberrant Histone Modification in Cancer ROLE OF MICRORNA IN CANCER Inactivation or Amplification of miRNA Genes A Transcriptional Control Mechanism for miRNAs Dysregulated Epigenetic Changes Role of Altered miRNA Expression in Cancer CHROMATIN REMODELING COMPLEXES AND CANCER EPIGENETICALLY SILENCED GENES: THE MOLECULAR ANATOMY ONCOGENIC PRODUCTS DISRUPT THE EPIGENETIC MACHINERY EPIGENETIC THERAPY SUMMARY CONCLUSION CONSENT FOR PUBLICATION CONFLICT OF INTEREST ACKNOWLEDGEMENTS REFERENCES Subject Index Back Cover