Resistance to targeted therapies in multiple myeloma / / Silvia Cw Ling, Steven Trieu, editors

• Pubblicazione: Cham, Switzerland : , : Springer, , [2021]; ©2021
• Descrizione fisica: 1 online resource (161 pages)
• Disciplina: 616.994061
• Soggetto topico: Drug resistance in cancer cells; Multiple myeloma - Treatment; Mieloma múltiple; Resistència als medicaments
• Soggetto genere / forma: Llibres electrònics
• Persona (resp. second.): LingSilvia Cw; TrieuSteven
• Nota di contenuto: Intro -- Aims and Scope -- Objective -- Preface -- Contents -- Series Editor Biography -- About the Series Editor -- Contributors -- About the Editors -- Chapter 1: The Role of Targeted Therapy in Multiple Myeloma -- 1.1 Multiple Myeloma Overview -- 1.2 Historical Treatment of Multiple Myeloma Until Present -- 1.3 Immunomodulatory Imide Drugs -- 1.4 Proteasome Inhibitors -- 1.5 Monoclonal Antibodies -- 1.6 Histone Deacetylase Inhibitors -- 1.7 Bone Targeted Therapy -- 1.8 New Agents on the Horizon -- 1.9 Conclusion -- References -- Chapter 2: Lenalidomide -- 2.1 Introduction -- 2.2 Indications -- 2.3 Efficacy of Lenalidomide -- 2.3.1 Efficacy in Relapsed or Refractory Multiple Myeloma -- 2.3.1.1 Lenalidomide and Dexamethasone -- 2.3.1.2 Bortezomib, Lenalidomide, and Dexamethasone -- 2.3.1.3 Daratumumab, Lenalidomide, and Dexamethasone -- 2.3.1.4 Carfilzomib, Lenalidomide, and Dexamethasone -- 2.3.2 Efficacy in Newly Diagnosed Multiple Myeloma -- 2.3.2.1 Transplant Ineligible Patients -- Lenalidomide and Dexamethasone -- Cyclophosphamide, Lenalidomide, and Dexamethasone -- Bortezomib, Lenalidomide, and Dexamethasone -- 2.3.2.2 Transplant Eligible Patients -- Bortezomib, Lenalidomide, and Dexamethasone -- 2.4 Mechanisms of Action -- 2.4.1 Cereblon Pathway -- 2.4.2 Effect on Cytokines -- 2.4.3 T Cell Activation -- 2.4.4 Effect on Natural Killer Cells -- 2.4.5 Anti-Angiogenic Activity -- 2.4.6 Direct Antitumor Activity -- 2.4.7 Myeloma Microenvironment -- 2.5 Lenalidomide Resistance -- 2.5.1 Potential Mechanisms of Lenalidomide Resistance -- 2.5.1.1 Decreased Cereblon Expression and Downstream Factors -- 2.5.1.2 Increase in c-Myc -- 2.5.2 Management of Lenalidomide-Resistant Disease -- 2.5.2.1 Pomalidomide-Based Regimes -- 2.5.2.2 Proteasome Inhibitor and Daratumumab-Based Regimes -- 2.6 Conclusion -- References -- Chapter 3: Pomalidomide. ; 3.1 Introduction -- 3.2 Clinical Indication of Pomalidomide -- 3.3 Efficacy -- 3.3.1 Efficacy in Relapsed and Refractory Multiple Myeloma -- 3.3.1.1 Pomalidomide and Dexamethasone -- 3.3.1.2 Pomalidomide + Dexamethasone + Cyclophosphamide -- 3.3.1.3 Pomalidomide, Bortezomib, and Dexamethasone -- 3.3.1.4 Pomalidomide, Daratumumab, and Dexamethasone -- 3.3.1.5 Pembrolizumab, Pomalidomide, and Dexamethasone -- 3.4 Mechanisms of Pomalidomide Action -- 3.5 Potential Mechanism of Pomalidomide Resistance and Overcoming Resistance -- 3.6 Conclusion -- References -- Chapter 4: Mechanisms Driving Resistance to Proteasome Inhibitors Bortezomib, Carfilzomib, and Ixazomib in Multiple Myeloma -- 4.1 Introduction -- 4.2 The Proteasome -- 4.3 Endoplasmic Reticulum Stress -- 4.4 Proteasome Inhibitors in Multiple Myeloma -- 4.5 Bortezomib Resistance Mechanisms -- 4.5.1 Proteasome Mutation and Overexpression -- 4.5.2 Drug Efflux -- 4.5.3 Plasma Cell Differentiation -- 4.5.4 Upregulation of Heat Shock Proteins -- 4.5.5 Autophagy -- 4.5.6 The Bone Marrow Microenvironment -- 4.6 Resistance Mechanisms to Second Generation Proteasome Inhibitors -- 4.6.1 Carfilzomib Resistance Mechanisms -- 4.6.1.1 Proteasome Mutations -- 4.6.1.2 Drug Efflux -- 4.6.1.3 Autophagy -- 4.6.1.4 Bone Marrow Microenvironment -- 4.6.2 Ixazomib Resistance Mechanisms -- 4.7 Conclusion -- References -- Chapter 5: Daratumumab -- 5.1 Introduction -- 5.2 Mechanism of Action -- 5.3 Mechanisms Behind Daratumumab-Resistance -- 5.3.1 Reduced Cell Surface Expression of Target Antigen CD38 -- 5.3.2 Antibody-Dependent Cell Cytotoxicity Resistance -- 5.3.3 Antibody-Dependent Cellular Phagocytosis Resistance -- 5.3.4 Complement-Dependent Cytotoxicity Resistance -- 5.3.5 Immune Modulated Resistance -- 5.4 Clinical Efficacy of Daratumumab -- 5.4.1 Daratumumab in the Relapsed and Refractory Setting. ; 5.4.2 Daratumumab in Newly Diagnosed, Transplant Ineligible Patients -- 5.4.3 Daratumumab in Newly Diagnosed, Transplant Eligible Patients -- 5.5 Toxicity Profile -- 5.6 Conclusion -- References -- Chapter 6: Elotuzumab -- 6.1 Introduction -- 6.2 Mechanisms of Action -- 6.2.1 Preclinical Studies -- 6.3 Pharmacological Characteristics of Elotuzumab -- 6.4 Mechanisms of Resistance to Elotuzumab -- 6.4.1 Expression of the Antigen Target of the Monoclonal Antibody -- 6.4.2 CD16a Expression on NK Cells and Associated Polymorphisms -- 6.4.3 Interactions with the Microenvironment -- 6.4.4 Development of Neutralizing Antibodies -- 6.5 Clinical Trials -- 6.5.1 Relapsed and/or Refractory Myeloma -- 6.6 Toxicities of Elotuzumab -- 6.7 Conclusion -- References -- Chapter 7: Histone Deacetylase Inhibitors -- 7.1 Introduction -- 7.2 Histone Deacetylases -- 7.2.1 Class I Histone Deacetylases -- 7.2.2 Class II Histone Deacetylases -- 7.2.3 Class III Histone Deacetylases (Sirtuins) -- 7.2.4 Class IV Histone Deacetylases -- 7.3 Histone Deacetylases in Multiple Myeloma -- 7.3.1 Histone Deacetylases and Protein Clearance -- 7.3.2 Histone Deacetylase Overexpression and Increased Activity in Multiple Myeloma -- 7.4 Histone Deacetylase Inhibitors -- 7.4.1 Types of Histone Deacetylase Inhibitors -- 7.4.2 Mechanisms of Action -- 7.4.2.1 Altered Gene Expression -- 7.4.2.2 Induction of Apoptosis -- 7.4.2.3 Cell Cycle Arrest -- 7.4.2.4 Inhibition of Angiogenesis -- 7.4.2.5 Regulation of Cytokines -- 7.4.2.6 Suppressed DNA Damage Repair -- 7.4.2.7 Ubiquitin Proteasome System -- 7.4.2.8 Aggresome Pathway -- 7.5 Approved Histone Deacetylase Inhibitors -- 7.5.1 Panobinostat -- 7.5.2 Vorinostat -- 7.5.3 Ricolinostat -- 7.6 Immunomodulatory Imide Drugs and Histone Deacetylase Inhibitors -- 7.7 Potential Mechanisms of Resistance to Histone Deacetylase Inhibitors. ; 7.7.1 Drug Transporters -- 7.7.2 Cell Signaling -- 7.7.3 Antioxidant Pathway -- 7.7.4 Cell Cycle Proteins -- 7.7.5 Nuclear Factor-Kappa B -- 7.7.6 Anti-Apoptotic Proteins -- 7.7.7 Altered Histone Deacetylases -- 7.7.8 Autophagy -- 7.8 Conclusion -- References -- Chapter 8: Bone Targeted Therapies -- 8.1 Myeloma Bone Disease -- 8.1.1 Diagnosis -- 8.1.2 Pathogenesis -- 8.1.3 Osteoclastic Activation -- 8.1.3.1 The RANK/RANKL Pathway -- 8.1.3.2 Interleukins -- 8.1.3.3 Hepatocyte Growth Factor -- 8.1.3.4 Notch Pathway -- 8.1.3.5 Chemokines -- 8.1.3.6 Activin A -- 8.1.3.7 The TNF Superfamily -- 8.1.3.8 BTK and SDF-1α -- 8.1.4 Osteoblastic Suppression -- 8.1.4.1 The WNT Pathway -- 8.1.4.2 Sclerostin -- 8.1.4.3 DKK1 -- 8.1.4.4 Periostin -- 8.1.4.5 RUNX2/CBFA1 and IL-7 -- 8.2 Indications for Bone Targeted Therapies -- 8.3 Utility of Bone Resorption Markers to Guide Therapy -- 8.4 Current Treatments for Myeloma Bone Disease -- 8.4.1 Bisphosphonates -- 8.4.1.1 Mechanism of Action -- 8.4.1.2 Evidence in MBD -- 8.4.1.3 Comparison Between Bisphosphonates -- 8.4.1.4 Adverse Events -- 8.4.1.5 Renal Impairment -- 8.4.1.6 Osteonecrosis of the Jaw -- 8.4.1.7 Subtrochanteric and Other Atypical Femoral Fractures -- 8.4.1.8 Duration, Frequency, and Monitoring of Therapy -- 8.4.1.9 Future of Bisphosphonate Therapy -- 8.4.2 Denosumab -- 8.4.2.1 Mechanism of Action -- 8.4.2.2 Evidence in MBD -- 8.4.2.3 Adverse Events -- 8.4.2.4 Duration and Frequency of Therapy -- 8.4.3 Novel Therapies -- 8.4.3.1 Anti-Sclerostin Antibodies -- 8.4.3.2 Anti-DKK1 Neutralizing Antibodies -- 8.4.3.3 Activin Receptor Ligand Traps -- 8.4.3.4 Bruton's Tyrosine Kinase (BTK) Inhibitors -- 8.4.3.5 B Cell Activating Factor (BAFF) Neutralizing Antibodies -- 8.4.3.6 Transforming Growth Factor-β (TGF-β) Inhibitors -- 8.4.3.7 Parathyroid Hormone -- 8.4.3.8 Proteasome Inhibitors. ; 8.4.3.9 Immunomodulatory Imide Drugs -- 8.5 Conclusion -- References -- Chapter 9: New Targeted Therapies for Multiple Myeloma Under Clinical Investigation -- 9.1 Introduction -- 9.2 Antibodies -- 9.2.1 Monoclonal Antibodies Directed at Plasma Cells -- 9.2.2 Bispecific Antibodies -- 9.2.3 Checkpoint Inhibitor -- 9.2.4 Cellular Therapies -- 9.2.4.1 Chimeric Antigen Receptor T Cells -- 9.2.4.2 DC Vaccination -- 9.2.5 Small-Molecule Inhibitors -- 9.2.5.1 Targeting Specific Subsets of Patients -- Venetoclax for Patients with Chromosomal Translocation t(11 -- 14) -- Patients with BRAF V600E Mutation -- Potential MEK Inhibition -- 9.2.5.2 Patients with Overexpressed FGFR3 -- 9.2.5.3 Targeting Inherent Weaknesses in MM -- SINE Compounds -- Bromodomain Inhibitors -- Kinesin Spindle Protein Inhibitors -- 9.3 Conclusion and Perspectives -- References -- Index.
• Titolo autorizzato: Resistance to Targeted Therapies in Multiple Myeloma
• ISBN: 3-030-73440-4
• Formato: Materiale a stampa
• Livello bibliografico: Monografia
• Lingua di pubblicazione: Inglese
• Record Nr.: 9910495203303321
• Lo trovi qui: Univ. Federico II
• Serie: Resistance to targeted anti-cancer therapeutics ; ; Volume 22.