Linked e-resources
Details
Table of Contents
Contributors; Chapter-1; Melanoma: Historical Context; 1.1 Introduction; 1.2 Epidemiologic Trends; 1.3 Evolution in Surgical Management; 1.4 Adjuvant Therapy; 1.5 Evolution of Systemic Treatment Approaches; 1.6 Immunotherapy; 1.7 Conclusion; References; Chapter-2; Melanoma Pathogenesis; 2.1 Melanocyte Biology; 2.2 Melanoma Risk Factors; 2.3 MAPK and PI3K Pathways; 2.4 RB and p53 Pathways; 2.5 MITF; 2.6 Acral and Mucosal Melanomas; 2.7 Uveal Melanoma; 2.8 Melanoma Genomics; 2.9 Conclusion; References; Chapter-3; Molecular Diagnostics and Tumor Mutational Analysis; 3.1 Introduction
3.2 Somatic Mutations in Melanoma3.2.1 UV Damage-Induced Mutations; 3.2.2 BRAF Mutations; 3.2.3 NRAS Mutations; 3.2.4 KIT Mutations; 3.3 Somatic Mutation Testing-Technology; 3.3.1 Direct Sequencing; 3.3.2 Genomic Aberrations; 3.3.3 Massively Parallel Sequencing; 3.3.4 Results of Whole Exome Sequencing/Whole Genome Sequencing in Melanoma; 3.4 Conclusion; References; Chapter-4; Clinical Utility of BRAF-Targeted Therapy in Melanoma; 4.1 Introduction; 4.2 BRAF Inhibitors; 4.2.1 Sorafenib; 4.2.2 Vemurafenib; 4.2.2.1 Early Phase Studies; 4.2.2.2 Phase II/III Studies and Subsequent Experience
4.2.3 Dabrafenib4.2.3.1 Early Phase Trials; 4.2.3.2 Phase III Clinical Trial; 4.2.4 Encorafenib (LGX818); 4.2.5 Secondary Malignancies and Rare Toxicities; 4.2.6 Summary; 4.3 MEK Inhibitors; 4.3.1 Selumetinib; 4.3.2 Trametinib; 4.3.2.1 Early Phase Trials; 4.3.2.2 Phase III Trial; 4.3.2.3 Trametinib in BRAF Inhibitor-Resistance; 4.3.3 Binimetinib (MEK162); 4.3.4 Conclusions; 4.4 Combination Therapy; 4.4.1 Rationale and Efficacy; 4.4.2 Toxicity; 4.4.3 Crossover; 4.4.4 Current Status of Combination Therapies; 4.4.5 Summary; 4.5 Special Clinical Situations
4.5.1 Targeted Therapy in Brain Metastases4.5.2 Treatment Beyond Progression; 4.5.3 Non-V600E Melanoma; 4.6 Conclusion and Future Directions; References; Chapter-5; The Ethics of Randomized Trials in Oncology; 5.1 Introduction; 5.2 A Brief History of Clinical Research in Humans: Selected Examples; 5.3 Ethical Guidelines for Clinical Research; 5.4 Clinical Trials: Research Questions and Study Design; 5.4.1 Advantages of Randomized Controlled Trials (RCTs); 5.4.2 Ethical Considerations in the Design of RCTs; 5.5 Ethical Issues in the Conduct of Clinical Trials
5.6 Special Issues in Oncology Clinical Trials5.7 Case Study: Ethical Issues in the BRIM-3 Trial; References; Chapter-6; Parallel and Serial Blockade Strategiesin BRAF-Mutant Melanoma; 6.1 Introduction; 6.2 Molecular Biology of Melanoma; 6.3 Development of BRAF Inhibitors; 6.4 Rationale for Dual Inhibition of the MAPK Pathway; 6.5 The PI3K-AKT Pathway as Combinatorial Target; 6.6 Other Targets and Oncogenes; 6.7 Summary and Future Directions; References; Chapter-7; Targeting the Cell Cycle and p53 in Combination with BRAF-Directed Therapy; 7.1 Introduction; 7.2 Cell Cycle
3.2 Somatic Mutations in Melanoma3.2.1 UV Damage-Induced Mutations; 3.2.2 BRAF Mutations; 3.2.3 NRAS Mutations; 3.2.4 KIT Mutations; 3.3 Somatic Mutation Testing-Technology; 3.3.1 Direct Sequencing; 3.3.2 Genomic Aberrations; 3.3.3 Massively Parallel Sequencing; 3.3.4 Results of Whole Exome Sequencing/Whole Genome Sequencing in Melanoma; 3.4 Conclusion; References; Chapter-4; Clinical Utility of BRAF-Targeted Therapy in Melanoma; 4.1 Introduction; 4.2 BRAF Inhibitors; 4.2.1 Sorafenib; 4.2.2 Vemurafenib; 4.2.2.1 Early Phase Studies; 4.2.2.2 Phase II/III Studies and Subsequent Experience
4.2.3 Dabrafenib4.2.3.1 Early Phase Trials; 4.2.3.2 Phase III Clinical Trial; 4.2.4 Encorafenib (LGX818); 4.2.5 Secondary Malignancies and Rare Toxicities; 4.2.6 Summary; 4.3 MEK Inhibitors; 4.3.1 Selumetinib; 4.3.2 Trametinib; 4.3.2.1 Early Phase Trials; 4.3.2.2 Phase III Trial; 4.3.2.3 Trametinib in BRAF Inhibitor-Resistance; 4.3.3 Binimetinib (MEK162); 4.3.4 Conclusions; 4.4 Combination Therapy; 4.4.1 Rationale and Efficacy; 4.4.2 Toxicity; 4.4.3 Crossover; 4.4.4 Current Status of Combination Therapies; 4.4.5 Summary; 4.5 Special Clinical Situations
4.5.1 Targeted Therapy in Brain Metastases4.5.2 Treatment Beyond Progression; 4.5.3 Non-V600E Melanoma; 4.6 Conclusion and Future Directions; References; Chapter-5; The Ethics of Randomized Trials in Oncology; 5.1 Introduction; 5.2 A Brief History of Clinical Research in Humans: Selected Examples; 5.3 Ethical Guidelines for Clinical Research; 5.4 Clinical Trials: Research Questions and Study Design; 5.4.1 Advantages of Randomized Controlled Trials (RCTs); 5.4.2 Ethical Considerations in the Design of RCTs; 5.5 Ethical Issues in the Conduct of Clinical Trials
5.6 Special Issues in Oncology Clinical Trials5.7 Case Study: Ethical Issues in the BRIM-3 Trial; References; Chapter-6; Parallel and Serial Blockade Strategiesin BRAF-Mutant Melanoma; 6.1 Introduction; 6.2 Molecular Biology of Melanoma; 6.3 Development of BRAF Inhibitors; 6.4 Rationale for Dual Inhibition of the MAPK Pathway; 6.5 The PI3K-AKT Pathway as Combinatorial Target; 6.6 Other Targets and Oncogenes; 6.7 Summary and Future Directions; References; Chapter-7; Targeting the Cell Cycle and p53 in Combination with BRAF-Directed Therapy; 7.1 Introduction; 7.2 Cell Cycle