Oncogenomics

From Basic Research to Precision Medicine
 
 
Elsevier (Verlag)
  • 1. Auflage
  • |
  • erschienen am 30. Oktober 2018
  • |
  • 718 Seiten
 
E-Book | ePUB mit Adobe DRM | Systemvoraussetzungen
E-Book | PDF mit Adobe DRM | Systemvoraussetzungen
978-0-12-811786-6 (ISBN)
 

Oncogenomics: From Basic Research to Precision Medicine offers a thorough survey of precision medicine and its diagnostic and therapeutic applications in oncology. Gathering contributions from leading international researchers in the field, chapters examine recent translational advances in oncogenomic methods and technologies, detail novel molecular classifications of tumors, and identify diagnostic and prognostic biomarkers for various types of cancers, including pancreatic, gastrointestinal, breast, hematological, lung, osteotropic, genitourinary, and skin cancers. This book provides a foundation for clinical oncologists, human geneticists, and physicians to develop new targeted cancer treatments and incorporate genomic medicine into clinical practice.

  • Provides clinical oncologists, human geneticists, physicians, and students with a thorough understanding of current diagnostic and prognostic applications of genomic methods and technologies to a variety of solid malignancies
  • Employs current knowledge in oncogenomics towards developing therapeutic interventions for various cancer types
  • Features a team of internationally recognized researchers and physicians in clinical oncology, oncogenomics and precision medicine
  • Englisch
  • Saint Louis
  • |
  • USA
  • 13,24 MB
978-0-12-811786-6 (9780128117866)
weitere Ausgaben werden ermittelt
  • Front Cover
  • Oncogenomics
  • Copyright Page
  • Dedications
  • Contents
  • List of Contributors
  • Preface
  • I. Molecular medicine: a novel approach to cancer investigation
  • 1 From the Double Helix to Oncogenomics and Precision Cancer Medicine: An Evolving Story
  • Abbreviations
  • The Double Helix and the Human Genome Project
  • Precision Medicine Initiative and Precision Cancer Medicine
  • Oncogenomics in the Fight Against Cancer
  • Master Protocols and Clinical Trials of Targeted Drugs
  • NSCLC and Melanoma: Successful Examples of Precision Cancer Medicine
  • NSCLC
  • Melanoma
  • Precision Cancer Medicine: Uncertainties and Drawbacks
  • Conclusions
  • References
  • 2 Intratumor Heterogeneity: Biological and Clinical Implications
  • Introduction
  • Levels of Intratumor Heterogeneity
  • Genetic Heterogeneity
  • Transcriptomic and Proteomic Heterogeneity
  • Spatial Heterogeneity
  • Phenotypic Heterogeneity
  • Clinical Implications of Intratumor Heterogeneity and Novel Approaches
  • Conclusions
  • Acknowledgments
  • References
  • 3 The Role of Proteomics in Cancer Research
  • What Is a Proteome?
  • Proteomics Approaches in Cancer Research
  • The Role of Proteomics in Cancer Research
  • Advantages of the Proteome in Understanding the Biology of Cancer
  • Applying Proteomics Tools for Cancer Research
  • Post-translational Modifications in Cancer
  • Tumor Biomarkers and Liquid Biopsy
  • Monitoring Drug Effects With Proteomics
  • Conflict of Interest
  • References
  • Further Reading
  • 4 Next-Generation Sequencing in Clinical Practice
  • References
  • Further Reading
  • 5 Cancer Epigenetics: Aberrant DNA Methylation in Cancer Diagnosis and Treatment
  • Introduction
  • DNA Methylation and Transcriptional Regulation
  • Alterations of DNA Methylation in Cancer Cells
  • The CpG Island Methylator Phenotype
  • Cancer Diagnosis Using Aberrant DNA Methylation
  • Cancer Detection Diagnosis
  • Diagnosis of Cancer Pathophysiology
  • Advantages of Pathophysiology Diagnosis Using Aberrant DNA Methylation
  • Cancer Risk Diagnosis
  • Cancer Therapy by Targeting Aberrant DNA Methylation
  • Importance of Treatment Dose and Schedule for DNA Demethylating Drugs
  • Mechanisms of DNA Demethylating Therapy
  • Applications of DNA Demethylating Therapy to Solid Tumors
  • Future Perspective of DNA Demethylating Therapy
  • Epilogue
  • References
  • 6 Cancer Stem Cells: Role in Tumor Progression and Treatment Resistance
  • Introduction
  • Role of Cancer Stem Cells in Tumor Progression
  • Cancer Stem Cells in Therapy Resistance
  • Mechanisms of Cancer Stem Cell Therapy Resistance
  • Conclusion
  • References
  • 7 Cancer Stem Cells, Apoptosis Pathways and Mechanisms of Death Resistance
  • Introduction
  • Cancer Stem Cells Phenotype
  • Cancer Stem Cells Signaling Pathways
  • Drug Resistance in CSCs
  • MicroRNAs and Other Epigenetic Factors in CSCs
  • Cancer Stem Cells and Apoptosis Pathways
  • Mitochondrial Pathway
  • Death Receptor Pathway
  • Endoplasmic Reticulum (ER) Stress-Induced Apoptosis Pathway
  • Mechanisms of Death Resistance in Cancer Stem Cells
  • Multidrug Resistance (MDR) Transporters
  • PI3K/Akt/mTOR Signaling Pathway Plays a Crucial Role in CSCs
  • Dysregulated Antiapoptotoic Proteins in CSCs
  • Bcl-2 Family of Proteins
  • TRADD Expression and NF-?B Activity
  • Inhibitor of Apoptosis (IAP) Family of Proteins in CSC
  • c-FLIP Overexpression in CSCs
  • Resistance to ER Stress-Induced Apoptosis in CSCs
  • Conclusions and Future Directions
  • Acknowledgments
  • References
  • 8 Targeting the Hedgehog and Notch Signaling Pathways in Cancer Stem Cells
  • Introduction
  • Hedgehog Pathway
  • Notch Pathway
  • Therapies Targeting Hedgehog and Notch Signaling in Cancer Stem Cells
  • Hedgehog Pathway Antagonists
  • Notch Pathway Antagonists
  • Conclusions and Future Perspectives
  • References
  • 9 Cancer Stem Cells in Multiple Myeloma and the Development of Novel Therapeutic Strategies
  • Abbreviations
  • Introduction
  • Multiple Myeloma Cancer Stem Cells: General Concepts
  • Clonotypic B Cells
  • Clonogenic Plasma Cells
  • Interconversion Between Differentiated and Undifferentiated Clonotypic Cells
  • Side Population Cells
  • Drug Resistance
  • Signaling Pathways
  • MicroRNAs
  • Bone Marrow Microenvironment
  • Targeting Multiple Myeloma Cancer Stem Cells
  • Conclusions
  • References
  • II. Oncogenomics: Circulating Biomarkers in Clinical Oncology
  • 10 Bone Metastases from Solid Tumors: In Search of Predictive Biomarkers for Clinical Translation
  • Abbreviations
  • Introduction
  • Epidemiological and Clinical Features of Bone Metastases
  • Pathogenesis of Bone Metastases
  • The "Omics Sciences" in the Prediction of Bone Metastases From Most Common Solid Cancers
  • In Search of a "Genomic Osteotropism Signature" in Solid Tumors
  • Prediction of Bone Metastases: A Clinical and Socioeconomic Issue
  • Conclusions
  • References
  • 11 Liquid Biopsy and Genomic Assessment for Lung Cancer: The Role in Clinical Practice?
  • Introduction
  • Which Biological Source?
  • Importance of the Preanalytical Steps for the Reliability of the Results
  • Which Analytical Platform for Which Evaluation?
  • Targeted Evaluation of Mutations in EGFR
  • Targeted Investigation Into Genomic Alterations Other That Those Present in EGFR
  • Detection With a Selected Panel of Genes
  • Perspectives and Conclusion
  • References
  • 12 Prognostic and Predictive Role of Circulating Tumor Cells
  • Introduction
  • CTC Isolation and Detection
  • Prognostic Role of CTCs in Solid Tumors
  • Enumeration and Analysis of CTCs to Predict Treatment Response in Solid Tumors
  • Clinical Utility of CTCs: Current Status and Future Directions
  • References
  • 13 Circulating miRNAs as Tumor Biomarkers
  • MicroRNAs: Biosynthesis and Function
  • miRNAs Dysregulated in Cancer
  • Extracellular Vesicles and Extracellular miRNAs
  • Circulating miRNAs as Potential Biomarkers for Cancers
  • Breast Cancer
  • Colorectal Cancer
  • Lung Cancer
  • Pancreatic Cancer
  • Challenges and Opportunities for miRNA Based Biomarkers
  • Acknowledgments
  • References
  • 14 Circulating DNA in Cancer Diagnosis and Prognosis
  • Introduction
  • Circulating Cell-Free DNA
  • Circulating Tumor DNA (ctDNA)
  • Circulating DNA Levels in Patients With Cancer
  • Circulating Mutant Tumor DNA
  • Presence of Mutant Circulating Tumor DNA as a Prognostic Marker
  • Mutant Circulating Tumor DNA to Identify Therapy Sensitive or Resistant Cancer Subpopulations
  • Direct Comparison of Cancer Tissue DNA Mutations and Circulating Tumor DNA Mutations
  • Healthy Cells Can Take Up Mutant ctDNA
  • Copy Number Variations in Circulating Tumor DNA
  • Gene Methylation in Circulating Tumor DNA
  • Conclusions
  • References
  • 15 Sequencing a Single Circulating Tumor Cell for Genomic Assessment
  • Single-Cell Whole-Genome Sequencing Technologies
  • Isolation of a Single CTC
  • Single-Cell Whole-Genome Amplification Methods
  • Linker Adapter PCR
  • Primer Extension Preamplification PCR
  • Degenerate Oligonucleotide-Primed Polymerase Chain Reaction
  • Multiple Displacement Amplification
  • Multiple Annealing and Looping-Based Amplification Cycles
  • Single CTC NGS for Genetic Study of CTCs and Clinical Applications
  • Challenges and Future Prospects
  • References
  • 16 Single Nucleotide Polymorphisms in Cancer Research and Treatment
  • Introduction
  • Potential Applications of SNPs in Oncology: Tumor Susceptibility
  • Potential Applications of Snps in Oncology: Association With Prognosis
  • Potential Applications of SNPs in Oncology: Association With Treatment Outcome
  • References
  • III. Gastrointestinal tumors: molecular diagnosis and treatment
  • 17 Gastric Cancers: A Molecular Roadmap for Patient Stratification and Targeted Therapies
  • Introduction
  • Molecular Classification of Gastroesophageal Cancer
  • Microsatellite Instability as a Biomarker
  • Immuno-oncology Agent Biomarkers
  • Current and Potential Targeted Therapeutic Strategies
  • Receptor Tyrosine Kinase (RTK) Amplifications
  • Targeting DNA Damage Repair (DDR) Pathways
  • Antiangiogenesis Therapies
  • Immune Checkpoint Inhibition
  • Other Molecular Targets of Interest in Gastrointestinal Adenocarcinomas
  • Future Directions
  • References
  • Further Reading
  • 18 Resistance to EGFR Targeting Treatments in Colorectal Cancer
  • Anti-EGFR Therapeutic Strategies in Colorectal Cancer
  • Resistance to Anti-EGFR Therapies: Heterogeneity Matters
  • Mechanisms of Resistance
  • Mutations
  • Epigenetic Abnormalities
  • Microenvironment
  • Signaling Reactivation and Pathway Bypass
  • Conclusions
  • Acknowledgment
  • References
  • 19 Circulating DNA and Protein Biomarkers for the Treatment of Metastatic Colorectal Cancer with Tyrosine Kinase Inhibitors
  • Introduction
  • Mutational profiles and targeted therapies in metastatic colorectal cancer
  • TKIs and monoclonal antibodies in metastatic Colorectal Cancer
  • Tissue testing
  • Liquid biopsies in metastatic colorectal cancer
  • Circulating cell-free DNA in metastatic colorectal cancer
  • Plasma protein biomarkers to monitor the effect of TKI in metastatic colorectal cancer
  • Further research and the way forward
  • References
  • 20 Rationale for Immunotherapy in Gastrointestinal Malignancies
  • Introduction
  • Esophageal and Gastric Cancer
  • Anti-PD-1 Therapy in Gastroesophageal Cancer
  • Esophageal Squamous Cell Carcinoma
  • Colorectal Cancer
  • Pancreatic Cancer
  • Hepatocellular Carcinoma
  • Biliary Tract Cancer
  • Conclusions
  • References
  • Further Reading
  • 21 Proteomics Profiling of Pancreatic Cancer: Roles in Biomarker Discovery
  • Introduction
  • MS-Based Proteomics Methodologies
  • Global Proteomics Profiling in Cancer Biomarker Discovery
  • Candidate-Based Quantitative Analysis for Biomarker Detection
  • Recent Proteomics Discovery in Pancreatic Cancer
  • Pancreatic Tissue
  • Plasma/Serum
  • Pancreatic Juice
  • Cyst Fluid
  • Urine
  • Conclusion
  • Acknowledgment
  • References
  • 22 Emerging Technologies for the Diagnosis and Treatment of Pancreatic Cancer
  • Histopathologic and Molecular Diversity of Pancreatic Cancer
  • Conventional and Nanomedicine Treatment Strategies
  • Surgery and Chemotherapy
  • Nanotechnology-Based Drug Delivery
  • Personalized Medicine
  • Patient Stratification Based on Biomarkers
  • Patient Stratification Based on Noninvasive Imaging
  • Emerging Therapies and Diagnostics
  • Predictive Preclinical Models of PDAC Carcinogenesis
  • Image-Guided Surgery
  • Therapeutic Gene Silencing
  • Noninvasive Treatment Modalities
  • Diagnostics
  • Summary
  • Acknowledgment
  • References
  • Further Reading
  • 23 Personalized Medicine in Gastrointestinal Stromal Tumors
  • References
  • 24 Circulating MicroRNAs as Tumor Biomarkers in Hepatocellular Carcinoma
  • Background
  • Extracellularly Circulating miRNAs in HCC: Diagnostic Performance
  • Extracellularly Circulating miRNAs as Prognostic Markers in Patients With HCC
  • miRNAs Associated With Exosomes, Microvesicles, and High-density Lipoprotein: Different Function, Different Information as ...
  • Considerations on the Shift of Extracellular Circulating miRNAs Into the Clinic
  • Conclusions
  • References
  • IV. Perspectives in breast cancer genomics
  • 25 Gene Profiles in Breast Cancer: Translation to Clinical Medicine
  • The Clinical Problem
  • Molecular Diagnostic Tests Commercially Available
  • Clinical Utility of Molecular Diagnostic Tests and Open Questions
  • Gene Signatures Developed by the Milano Group
  • Molecular Subtypes Are Here to Stay
  • The FFPE Revolution: Unlocking Pathology Tissue Blocks
  • Puttings Things Together: The Development of FFPE-Resilient Metagene-Based Risk Predictors
  • Hints Also Come from in Vitro Models
  • Conclusion
  • Note
  • References
  • 26 Novel Biomarkers Predicting the Development of Bone Metastasis in Early Breast Cancer
  • Introduction
  • Expression Profile
  • Mutation Profile
  • miRNA
  • Biochemical Markers of Bone Turnover
  • Conclusions
  • References
  • 27 HER2-Positive Early Breast Cancer: Affordable Risks, Affordable Therapies, and New Developments
  • Introduction
  • Trastuzumab for Early HER2-Positive Breast Cancer
  • Trastuzumab and Landmark Achievements in Metastatic Disease
  • Adjuvant Setting
  • Neoadjuvant Setting
  • Trastuzumab Cardiotoxicity
  • Moving Beyond Trastuzumab for Early HER2-positive Breast Cancer
  • Need for Treatment Optimization
  • Escalated Anti-HER2 Strategies for Early BC
  • Extended Duration of Anti-HER2 Therapy
  • Dual HER2 Blockade
  • Deescalated Anti-HER2 Strategies
  • Shortened Trastuzumab Duration
  • De-escalated Chemotherapy
  • Conclusions
  • References
  • 28 Role of Circulating Tumor Cells in Breast Cancer Patients
  • Abbreviations
  • Cells Released by Solid Tumors as "Liquid Biopsy" in Breast Cancer
  • Clinical Validity of CTC Counts and Dynamic Changes in Metastatic Breast Cancer
  • Clinical Validity of CTCs with Epithelial-Mesenchymal Plasticity
  • Clinical Validity of CTCs in Nonmetastatic Breast Cancer
  • Clinical Utility of CTC Characterization
  • Conclusions and Future perspectives
  • References
  • 29 Overcoming Endocrine Resistance in Breast Cancer: mTOR Inhibitors and New Drugs
  • Introduction
  • Endocrine Therapy in Metastatic Breast Cancer
  • Hormone Resistance
  • Strategies to Overcome Hormone Resistance
  • Epigenetic Modifiers
  • Agents Targeting Angiogenesis, the FGFR Pathway, or Cross-Talk Between ER and EGFR, HER2
  • Antiangiogenic Agents
  • Agents Targeting the FGFR Pathway
  • Anti-HER2 Agents
  • Fulvestrant Combined with AIs
  • Next-Generation SERDs
  • Targeting the PI3K/Akt/mTOR Pathway
  • mTOR Inhibitors
  • PI3K Inhibitors
  • Dual PI3K/mTOR Inhibitors
  • Dual PI3K/IGF-1 Inhibitors
  • Dual mTorc1/2 Inhibitors
  • Akt Inhibitors
  • SGK1 Inhibitors
  • Targeting Cell Cycle
  • Cyclin-Dependent Kinase Inhibitors
  • PI3K/mTOR and Cycline-Dependent Kinases Inhibitors Combination Therapy
  • Inhibition of the Proteasome
  • Targeting Immune Response as a Novel Strategy to Delay or Overcome Hormone Resistance
  • Anti-PD-1/PD-L1 Agents
  • CK Inhibitors Combined with Checkpoint Inhibitors and Hormone Therapy
  • Epigenetic Therapy Combined with Checkpoint Inhibitors or Hormone Therapy
  • Stimulation and/or Modulation of the Immune Response by Cytokines Given in Addition to Hormone Therapy
  • Conclusion
  • References
  • 30 Explore Genomic Profiles for Triple-Negative Breast Cancer to Discover Drug Targets
  • Introduction
  • TNBC Gene Expression Profiling
  • TNBC Somatic Mutation Profiling
  • TNBC Copy Number Alteration Profiling
  • TNBC Methylation Profiling
  • TNBC microRNA Expression Profiling
  • Integrative TNBC Genomic Profiling
  • Deregulated Pathways in TNBC
  • Targeted Therapy for TNBC
  • Immunotherapy of TNBC
  • Conclusion and Perspectives
  • Acknowledgment
  • References
  • V. Lung cancer: role of genomics in clinical practice
  • 31 Gene Fusion in NSCLC: ALK, ROS1, RET, and Related Treatments
  • Introduction
  • NSCLC: Past and Future
  • ALK, ROS1, and RET: Roles in Normal Physiology and Cancer Development
  • Methods to Detect Gene Fusions
  • Target Therapy Against Fused Genes in NSCLC
  • ALK Inhibitors
  • ROS1 Inhibitors
  • RET Inhibitors
  • Future Perspectives
  • References
  • 32 Circulating Tumor Cells and ctDNA in NSCLC: A Role for Treatment Decision
  • Introduction
  • Circulating Tumor DNA
  • Circulating Tumor Cells
  • Conclusions
  • References
  • 33 EGFR Mutations: Best Results from Second- and Third-Generation Tyrosine Kinase Inhibitors
  • Introduction
  • Second-Generation EGFR TKIs
  • Afatinib
  • Dacomitinib
  • Neratinib
  • Third-Generation EGFR TKIs
  • Conclusions
  • References
  • Further Reading
  • 34 Immuno-Oncology in Lung Cancer: A Focus on Anti-PD-1 and Anti-CTLA-4 Therapy in NSCLC
  • Introduction
  • Molecular Mechanism of Immuno-Oncology Therapies
  • Programmed Cell Death Protein 1(PD-1) Pathway in NSCLC
  • Combination Therapy With PD-1/PD-L1 Inhibitors
  • Targeting Cytotoxic T-Lymphocyte Associated Protein 4 in NSCLC
  • Conclusion
  • References
  • VI. Genomics in Genitourinary Cancer
  • 35 Molecular Assessment of Ovarian Cancer and Translation to Clinical Management
  • Introduction
  • Clinical Patterns of Ovarian Cancer
  • Molecular Patterns of Ovarian Cancer
  • Inherited Ovarian Cancer
  • High-Grade Serous Ovarian Cancer
  • Low-Grade Serous Ovarian Cancer
  • Clear Cell Carcinoma
  • Endometrioid Carcinoma
  • Mucinous Carcinoma
  • Nonepithelial Ovarian Cancer
  • Epigenetic Factors in Ovarian Cancer
  • Targeted Therapy of Ovarian Cancer
  • Angiogenesis Inhibitors
  • Bevacizumab
  • Pazopanib
  • Cediranib
  • PARP Inhibitors
  • HER2 Inhibitors
  • Antiepigenetic Approaches to Ovarian Cancer
  • Conclusion
  • References
  • Further Reading
  • 36 Development of PARP Inhibitors for BRCA-Deficient Epithelial Ovarian Cancer
  • Introduction
  • DNA Repair Pathways
  • PARP and DNA Repair
  • Clinical Applications of PARP Inhibitors
  • Early Phase Trials of PARP Inhibitors in Ovarian Cancer
  • Clinical Approvals for Olaparib in Ovarian Cancer
  • Rucaparib in Ovarian Cancer
  • Niraparib in Ovarian Cancer
  • Predictive Biomarkers for PARP Inhibitors
  • Conclusions
  • References
  • 37 New Treatment Options for Ovarian Cancer
  • Introduction
  • Molecular Analysis and Emerging Therapeutics in Ovarian Cancer
  • Targeted Therapy in Ovarian Cancer
  • PARP Inhibitors
  • Antiangiogenic Therapies: Bevacizumab
  • Emerging Therapeutic Considerations
  • References
  • 38 Emerging Immunotherapies for Renal Cell Carcinoma
  • Nivolumab
  • Ipilimumab
  • Pembrolizumab
  • Anti-PD-L1 Antibodies
  • Combination Strategies With Conventional Treatments
  • Adjuvant Treatments
  • References
  • 39 TKIs in Renal Cell Carcinoma: What Can We Expect in the Future?
  • Introduction
  • Renal Cell Carcinoma
  • TKIs Used in Clear Cell Renal Cell Carcinoma (ccRCC)
  • Sunitinib
  • Sorafenib
  • Pazopanib
  • Axitinib
  • Cabozantinib
  • First-Line Treatment
  • Second-Line Treatment
  • Levantinib
  • Second-Line Treatment
  • TKIs Within Treatment of Nonclear cell RCC
  • Adjuvant or Not?
  • Combining TKIs With Immunotherapies
  • Biomarkers for Use Within Treatment of RCC
  • Toxicities and Intermittent Therapy
  • References
  • 40 Circulating Tumor Cells as Surrogate Biomarker for Overall Survival in Metastatic Prostate Cancer
  • Introduction
  • Biology of Circulating Tumor Cells
  • Current Approaches for CTC Detection
  • CTCs as Surrogate Biomarker for Prostate Cancer in the Clinic
  • Challenges and Future Aspects When Including CTC Analysis in the Clinic
  • Conclusion
  • References
  • VII. Genomics in Neuroendocrine Tumors, Melanoma, and Sarcoma
  • 41 Management of NETs in the Precision Medicine Era
  • Introduction
  • Clinical Heterogeneity of NETs
  • Genomic Heterogeneity of NETs
  • Pancreatic NETs
  • Small Bowel NETs
  • Lung NETs
  • Innovative Approaches for the Diagnosis and Follow-Up of NETs
  • Systemic Treatment of Metastatic NETs: Towards Personalized Medicine Strategies
  • Palliation of Hormonal Symptoms
  • Precision Medicine Approaches
  • Control of Tumor Growth
  • Somatostatin Analogs
  • Precision Medicine Approaches
  • Radiolabeled Somatostatin Analogs
  • Precision Medicine Approaches
  • Biologic Agents
  • Precision Medicine Approaches
  • Chemotherapy
  • Precision Medicine Approaches
  • Immunotherapy
  • Precision Medicine Approaches
  • Conclusions
  • References
  • Further Reading
  • 42 Immunological and Genetic Biomarkers of Sarcomas: Implication for Future Treatment Strategies
  • The Sarcoma Scenario
  • Background of Immunotherapy in Sarcomas
  • Tumor-Host Interplay
  • Immune Infiltrate
  • Cytokines
  • Antigen Presentation
  • Metabolism
  • Therapeutic Strategies to Overcome Immune Tolerance
  • Angiogenesis
  • Increased Immunogenicity
  • Adoptive Cell Therapy
  • Conclusions
  • References
  • 43 Advances in Sarcoma Genomics and Therapeutic Management
  • Soft Tissue Sarcoma
  • Kinase Mutation
  • Recurrent Chromosomal Translocation
  • Gene Amplification
  • Loss of Tumor Suppressor Genes
  • Complex Genomics
  • Bone Sarcoma
  • Sarcoma in Hereditary Cancer Predisposition Syndromes
  • Li-Fraumeni Syndrome
  • Neurofibromatosis Type 1
  • Hereditary Retinoblastoma Syndrome
  • GIST Predisposition Syndromes
  • Tuberous Sclerosis Complex
  • Management of Specific Sarcomas Accounting for the Possibility of Inherited Cancer Predisposition
  • GIST
  • Osteosarcoma
  • Rhabdomyosarcoma
  • Soft Tissue Sarcomas
  • Conclusion
  • References
  • Further Reading
  • 44 Molecular Pathways in Melanomagenesis: Characterization of New Therapeutic Targets
  • Introduction to Melanoma: Classification, Epidemiology, and Clinical Course
  • Biology and Pathology of Melanoma
  • Cutaneous Melanoma
  • Ocular and Mucosal Melanoma
  • Fundamental Pathways Driving Melanoma Initiation and Progression
  • Cell signaling Pathways in Cutaneous Melanoma
  • RAS/RAF/MEK/ERK Pathway
  • PI3K/AKT/mTOR Pathway
  • Developmental Pathways: WNT/ß-Catenin and Notch
  • Cell Cycle and Apoptosis
  • Melanocyte-lineage specific pathway: the MITF axis
  • Crossroads Between Signaling Pathways and Immune Function
  • Cell Signaling Pathways in Uveal and Mucosal Melanoma
  • Targeted Therapies Approved for Melanoma Treatment
  • The Mutational Signature of Melanoma and Characterization of Novel Therapeutic Targets
  • The Genomic Landscape and Mutational Signature of Melanoma
  • Discovery of Candidate Pathways for Molecularly Targeted Strategies in Melanoma
  • Targeted Therapies in Clinical Development for Melanoma
  • Conclusive Remarks and Perspectives
  • References
  • Further Reading
  • 45 Immunotherapies and Novel Combinations: Advances in the Treatment of Melanoma
  • Introduction
  • Ipilimumab
  • Anti-PD-1 Agents (Nivolumab and Pembrolizumab)
  • Combined Anti-PD-1 and anti-CTLA-4 Therapy
  • Combination of Anti-PD-1/Anti-CTLA-4 Therapy With Other Immunotherapies
  • Combination of Immunotherapy With BRAF or MEK Inhibitors
  • Combination of Immunotherapy With Other Treatment Modalities
  • Conclusions
  • References
  • 46 BRAF-Mutant Melanoma: Treatment Approaches and Resistance Mechanisms
  • Introduction
  • Targeted Inhibition With BRAF and MEK Inhibitors
  • BRAF and MEK Inhibitor Resistance Mechanisms
  • Immune Therapy in BRAF-Mutant Patients
  • Future Therapies
  • Conclusion
  • Acknowledgments
  • References
  • Index
  • Back Cover

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