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ویرایش: نویسندگان: Owen A. O'Connor, Stephen M. Ansell, John F. Seymour سری: ISBN (شابک) : 111981992X, 9781119819929 ناشر: Wiley-Blackwell سال نشر: 2023 تعداد صفحات: 513 [514] زبان: English فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود) حجم فایل: 11 Mb
در صورت تبدیل فایل کتاب Precision Cancer Therapies, Volume 1: Targeting Oncogenic Drivers and Signaling Pathways in Lymphoid Malignancies: From Concept to Practice به فرمت های PDF، EPUB، AZW3، MOBI و یا DJVU می توانید به پشتیبان اطلاع دهید تا فایل مورد نظر را تبدیل نمایند.
توجه داشته باشید کتاب درمان های دقیق سرطان، جلد 1: هدف قرار دادن رانندگان سرطان زا و مسیرهای سیگنالینگ در بدخیمی های لنفاوی: از مفهوم تا عمل نسخه زبان اصلی می باشد و کتاب ترجمه شده به فارسی نمی باشد. وبسایت اینترنشنال لایبرری ارائه دهنده کتاب های زبان اصلی می باشد و هیچ گونه کتاب ترجمه شده یا نوشته شده به فارسی را ارائه نمی دهد.
مجموعه ای کامل از بسیاری از پیشرفت های علمی در توسعه مداوم درمان های سرطان دقیق مرتبط با لنفوم که رانندگان انکوژنیک و مسیرهای سیگنال دهی در بدخیمی های لنفاوی را هدف قرار می دهد: از مفهوم تا عمل بر روی لنفوم تمرکز دارد، منطقه ای که تعداد قابل توجهی از پیشرفت ها را به خود دیده است. توسعه درمان های دقیق سرطان هر بخش در یک زیست شناسی خاص یا دسته ای از داروها دارای یک فصل مقدماتی است که توسط یک مرجع در این زمینه نوشته شده است که منحصراً بر علم و ارتباط آن با بیولوژی سرطان متمرکز شده است. این رویکرد به نیاز دانشمندان، پزشکان و بخش خصوصی برای درک زمینه گستردهتر پیشرفتهای خارقالعادهای که چنین پیشرفتهای خیرهکنندهای را در این بیماری ایجاد کرده است، میپردازد. این کار در درجه اول بر چگونگی درک و ترجمه اصول بنیادی علوم پایه به اطلاعاتی متمرکز است که می تواند مستقیماً برای بیماران اعمال شود - از این رو عنوان فرعی، از مفهوم تا عمل. برای کمک به درک خوانندگان، صفحه اول هر فصل حاوی کادری با عنوان «امتیازهای خانه» است. این متن کوتاه نکات منحصر به فرد اصلی در مورد اطلاعات موجود در فصل را برجسته می کند. برخی از موضوعات کلیدی مورد بررسی در این کار به شرح زیر است: مبانی بیولوژیکی بدخیمی های لنفوئیدی: اصول اساسی لنفوموژنز و طبقه بندی مولکولی بدخیمی های لنفوئیدی هدف قرار دادن مرگ برنامه ریزی شده سلولی: اصولی برای درک بسیاری از انواع مرگ سلولی و ترکیبات امیدبخش از داروهای هدفمند. آپوپتوز هدف قرار دادن مسیر PI3K: درک پیچیدگی های این زیست شناسی پیچیده و دقیقاً چگونگی استفاده از داروهای هدفمند از نظر درمانی هدف قرار دادن اپی ژنوم سرطان: ویژگی های دارویی داروهایی که اپی ژنوم را هدف قرار می دهند و چشم اندازهای آینده برای هدف قرار دادن جنبه های مختلف کنترل اپی ژنتیکی هدف قرار دادن تومور مکانیسمهای تخریب پروتئین در سرطان شامل داروهای قدیمیتر مانند مهارکنندههای پروتئازوم و رویکردهای جدیدتر مبتنی بر PROTAC که عمدتاً برای دانشمندان و پزشکان در بخشهای دولتی و خصوصی، هدف قرار دادن رانندگان سرطانزا و مسیرهای سیگنالدهی در بدخیمیهای لنفاوی نوشته شده است: از مفهوم تا عمل کار مرجع جامع برای کسانی که علاقه مند به حوزه رو به رشد درمان های دقیق سرطان هستند. این جلد با ادغام یکپارچه علوم پایه و کاربردی، مرجعی ضروری برای کسانی خواهد بود که علاقه مند به ترجمه مهم ترین پیشرفت های علم به درمان های بدیع برای بیماران هستند.
A Thorough Compilation of the Many Scientific Breakthroughs in the Ongoing Development of Precision Cancer Therapies Related to Lymphoma Targeting Oncogenic Drivers and Signaling Pathways in Lymphoid Malignancies: From Concept to Practice focuses on lymphoma, an area which has seen a remarkable number of breakthroughs in the ongoing development of precision cancer therapies. Each section on a specific biology or class of drugs has an introductory chapter written by an authority in the field, exclusively focused on the science and its relevance to cancer biology. This approach addresses the need for scientists, physicians, and the private sector to understand the broader context of the extraordinary advances that have produced such astonishing advances in the disease. The work primarily focuses on how to understand and translate fundamental principles of basic science into information that can be directly applied to patients – hence the subtitle, From Concept to Practice. To aid in readers’ comprehension, the first page of each chapter contains a box entitled ‘Take Home Points’. This short text will highlight the major unique points about the information contained within the chapter. Some of the key topics addressed in the work are as follows: Biological basis of the lymphoid malignancies: fundamental principles of lymphomagenesis and molecular classification of lymphoid malignancies Targeting programmed cell death: principles for understanding the many types of cell death and promising combinations of drugs targeting apoptosis Targeting the PI3K pathway: understanding the intricacies of this complex biology and precisely how targeted drugs can be leveraged therapeutically Targeting the cancer epigenome: pharmacologic features of drugs targeting the epigenome and future prospects for targeting various aspects of epigenetic control Targeting the tumour proteome: understanding the mechanisms of protein degradation in cancer including both older drugs like proteasome inhibitors, and newer PROTAC based approaches Written primarily for scientists and physicians in both the public and private sectors, Targeting Oncogenic Drivers and Signaling Pathways in Lymphoid Malignancies: From Concept to Practice is a comprehensive reference work for those interested in the growing area of Precision Cancer Therapies. Seamlessly integrating the basic and applied science, this volume will be an indispensable reference for those interested in translating the most important advances in science to innovative novel treatments for patients.
Precision Cancer Therapies Contents List of Contributors Volume Foreword Volume Preface Series Preface Section I Biological Basis of the Lymphoid Malignancies 1 Fundamental Principles of Lymphomagenesis Take Home Messages Introduction How to Study Lymphomagenesis Before Lymphoma: The Gray Frontier Between Physiology and Pathology Driver Without Disease From In Situ Neoplasms to Asymptomatic Lymphomas Chronic Antigenic Stimulation as an Early Step of Lymphomagenesis The Cell of Origin Concept: A Classification Based on Physiology What Are the Hallmarks of Lymphoma? Epigenetics and Metabolism Apoptosis Escape Proliferation TCR/BCR Signaling Immune Escape Trafficking Microenvironment Conclusion Must Read References References 2 Identifying Molecular Drivers of Lymphomagenesis Take Home Messages Introduction Sequencing and Bioinformatics Methods Functional Validation of Drivers Common Themes in B- and T-cell Lymphoma Genetic Landscapes of Lymphomas Mature B-cell Lymphomas T-cell Lymphomas Genomic Subgrouping Approaches in DLBCL Challenges of Incorporating Genomic Subgrouping Approaches in Clinical Trials Leveraging Underlying Pathophysiology to Inform Therapeutic Consideration Conclusion Must Read References References 3 Characterizing the Spectrum of Epigenetic Dysregulation Across Lymphoid Malignancies Take Home Messages Introduction: Epigenetics and Lymphoid Malignancies Dysregulation of DNA Methylation and Modification of Histone Proteins Genes Involved in Histone Modification Implicated in Lymphomagenesis Enhancer of Zeste Homolog 2 (EZH2) CREB-binding Protein (CREBBP) and Histone Acetyltransferase P300 (EP300) The H3K4 Methyltransferase Family The Bromodomain and Extra-Terminal Domain (BET) Family Genes Involved in DNA Methylation Implicated in Lymphomagenesis DNA Methyltransferase 3A (DNMT3A) Ten-Eleven Translocation 1/2 (TET1/2) Isocitrate Dehydrogenase 2 (IDH2) The Epigenetic Landscape of Specific Lymphoid Malignancies Follicular Lymphoma Diffuse Large B-cell Lymphoma Marginal Zone Lymphoma Burkitt’s Lymphoma Acute Lymphoblastic Leukemia Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Hodgkin’s Lymphoma Multiple Myeloma Peripheral T-cell Lymphoma – Not Otherwise Specified Angioimmunoblastic T-cell Lymphoma and PTCL with TFH Phenotype Anaplastic Large Cell Lymphoma Adult T-cell Leukemia/Lymphoma Intestinal T-cell Lymphoma Hepatosplenic T-cell Lymphomas NK/T Cell Lymphoma Mycosis Fungoides and Sezary’s Syndrome Summary Must Read References References 4 Animal Models of Lymphoid Malignancies Take Home Messages Introduction Optimal Animal Models to Study Lymphoid Neoplasms Zebrafish Model Zebrafish Model of T-cell Neoplasms Zebrafish Model of B-cell Neoplasms Zebrafish Model of NK-cell Neoplasms Patient-Derived Xenograft Models in Zebrafish Fruit Fly Model Non-human Primate Model Mouse Models of Lymphoid Neoplasia Use of Animal Models in Translational Research Conclusions Must Read References References Section II Targeting the PI3 Kinase-AKT-mTOR Pathway 5 Principles of PI3K Biology and Its Role in Lymphoma Take Home Messages Introduction: Overview Four Decades of PI3K Signaling Research Class I PI3K Enzymes Isoforms Structural Organization Isoform-specific Functions The Essential Phospholipid Second Messenger PIP3 PI3K Pathway Effectors AKT, FOXO, and mTORC1 TEC Tyrosine Kinases Network Topology and Signal Robustness Dynamic PI3K Signaling in Lymphocyte Biology B-cell Development and Survival The Germinal Center (GC) Reaction TFH Cell Function Naïve and Effector T-cells Lessons from Monogenic Disorders Genetic PI3Kd Inactivation Genetic PI3Kd Hyperactivation Corrupted PI3K Signaling in Cancer The Success of PI3Kd Inhibition in Lymphoid Malignancies Quantitative Biology and Therapeutic Considerations Concluding Remarks Acknowledgments Must Read Reference References 6 Pharmacologic Differentiation of Drugs Targeting the PI3K-AKT-mTOR Signaling Pathway Take Home Messages Introduction PI3K Inhibitors Approved by the US Food and Drug Administration (FDA) PI3K Inhibitors in Clinical Development AKT Inhibitors mTOR Inhibitors Conclusions Must Read References References 7 Clinical Experience with Phosphatidylinositol 3-Kinase Inhibitors in Hematologic Malignancies Take Home Messages Introduction Idelalisib Copanlisib Duvelisib Umbralisib Parsaclisib Zandelisib Amdizalisib (HMPL-689) Conclusion Must Read References References 8 Clinical Experiences with Drugs Targeting mTOR Take Home Messages Introduction Rapamycin (Sirolimus) Rapamune® (Pfizer) and Generic Sirolimus The Rapamycin Analogs (Rapalogs) Temsirolimus (CCI-779; Torisel) Everolimus (RAD-001; Afinitor, Zortrees, Evertor) Summary of Lymphoma Studies of Everolimus Ridaforolimus Dual Inhibitors of mTORC1 and mTORC2 Side Effects of mTORC1 Inhibitors Future Directions for mTOR Inhibitors in Lymphoma Must Read References References 9 PI3 Kinase, AKT, and mTOR Inhibitors Take Home Messages Introduction PI3K Structure and Functions AKT Structure and Functions mTOR Structure and Functions PTEN as a Regulator of the PI3K/AKT/mTOR Pathway mTOR Inhibitors Temsirolimus: Phase 3 Trials PI3K and Dual PI3K/mTOR Inhibitors PI3K Isoforms and Expression Throughout the Body Immune Toxicity and Management Colitis Hepatitis Pneumonitis Skin Rash Homeostatic Toxicity Hypertension and Hyperglycemia Myelosuppression and Opportunistic Infection Myelosuppression Atypical Infection Vaccination Neuropsychiatric Problems PI3K Treatment in NHL AKT Inhibitors Conclusion Must Read References References Section III Targeting Programmed Cell Death 10 Principles for Understanding Mechanisms of Cell Death and Their Role in Cancer Biology Take Home Messages Introduction A Historical Perspective Apoptotic Pathways Other Cell Death Pathways The Role of Intrinsic Apoptosis in Normal Cells – Lessons from Gene Knockout Mice BCL2 Family Pro-survival Proteins BCL2 BCL-XL MCL-1 A1/BFL-1 BCL-W Combined Knockout of Pro-survival Proteins BCL2 Family Pro-apoptotic Effector Proteins BH3-only Proteins The Dysregulation of Apoptosis in Cancer Must Read References References 11 Pharmacologic Features of Drugs Targeting BCL2 Family Members Take Home Messages Introduction Historical Perspective: From the Discovery of BCL2 to Therapeutic Applications BCL2 as a Biomarker Targeting BCL2 Family Members Antisense Approaches for Targeting BCL2 Natural Anti-apoptotic Compounds Small Molecule Inhibitors of BCL2 Family Members Novel BCL2 Inhibitors on the Horizon Mechanisms of Resistance to BCL2 Inhibitors Novel Mechanisms to Overcome BCL2 Resistance Targeting MCL1 PROTAC Strategies for Targeting Apoptotic Family Members Conclusions Must Read References References 12 Clinical Experience with Pro-Apoptotic Agents Take Home Messages Introduction Safety and Toxicities of Pro-apoptotic Agents Tumor Lysis Syndrome Myeloid Compartment Toxicities and Infections Gastrointestinal Toxicities Thrombocytopenia and Navitoclax Efficacy of Venetoclax in Chronic Lymphocytic Leukemia/Small Cell Lymphoma Phase 1/2 Studies Combining Venetoclax with Conventional Chemotherapy in CLL/SLL Phase 3 Studies Venetoclax Re-treatment Efficacy of Venetoclax in Other B-cell Neoplasms Mantle Cell Lymphoma Follicular Lymphoma Diffuse Large B-cell Lymphoma and Other Aggressive B-cell Lymphomas Richter Transformation Waldenstrom’s Macroglobulinemia Marginal Zone Lymphoma Acute Lymphoblastic Leukemia/Lymphoma Lessons from Venetoclax in Lymphoid Neoplasms Other than CLL/SLL Associations and Mechanisms of Resistance to Pro-apoptotic Agents Must Read References References 13 Promising Combinations of Drugs Targeting Apoptosis Take Home Messages Introduction: Background and Disease Perspective Clinical Development of BCL2 Inhibitors Venetoclax Monotherapy for CLL Venetoclax Plus CD20 Monoclonal Antibody for CLL Venetoclax Plus BTK Inhibitor for CLL Venetoclax Plus BTK Inhibitor and CD20 Monoclonal Antibody for CLL Venetoclax Plus Chemoimmunotherapy Venetoclax Toxicities and Side Effects in CLL TLS Risk Mitigation and Management in CLL Venetoclax-associated Neutropenia Risk for Progression and Resistance Mechanisms Current Knowledge Gaps and Opportunities for Future Work with Venetoclax Must Read References References Section IV Targeting the Cancer Epigenome 14 The Role of Epigenetic Dysregulation in Lymphoma Biology Take Home Messages Introduction: Germinal Center B (GCB)-cells and GCB-derived Lymphomas Mutations Altering DNA Modifications and Structure TET2 Mutations Altering Writers of Histone Post-translational Modifications KMT2D CREBBP EZH2 Mutations Altering Higher Order Chromatin Structure BAF Chromatin Remodeling Complex Linker Histones Must Read References References 15 Quantitating and Characterizing the Effects of Epigenetic Targeted Drugs Take Home Messages Introduction Experimental Analysis of the Epigenome DNA Methylation Bisulfite Conversion Methods Affinity-based Methods Detection of 5hmC Histone Modifications, Histone Variants, and Chromatin-associated Proteins Antibody-based Techniques for Mapping the Chromatin State Proteomic Analysis of Histones Chromatin Accessibility Genome Organization Emerging Technologies for Epigenomic Analysis of Single Cells Molecular and Cellular Effects of Epigenetic Drugs Concluding Remarks Acknowledgments Must Read References References 16 Clinical Experience with Epigenetic Drugs in Lymphoid Malignancies Take Home Messages Introduction Epigenome and Cancer Different Epigenetic Classes of Drugs in Hematologic Malignancies DNMT Inhibitors 5-Azacytidine and Decitabine Guadecitabine HDAC Inhibitors Vorinostat Romidepsin Belinostat EZH2 Inhibitors Summary Must Read References References 17 Future Prospects for Targeting the Epigenome in Lymphomas Take Home Messages Introduction Emerging Epigenetic Therapies EZH2- and PRC2-targeted Therapies Are Emerging as Potential Cornerstone Therapies for Lymphomas SETD2, a Novel Therapeutic Target for DLBCLs LSD1, a Case of Bait and Switch A Surprising Indication for KDM5 Histone Demethylase Inhibitors New Opportunities Provided by Emerging Histone Deacetylase Inhibitors Sirtuins, the “Other HDACs,” Potential Therapeutic Targets in B-cell Lymphomas Histone Acetyltransferase Inhibitors, Lacking Selectivity but with Activity in Lymphomas Is There a Potential Role for BET Inhibitors for Lymphoma? DNA Methyltransferase Inhibitors Are Increasingly Relevant for Treatment of Lymphomas Nucleosome Remodeling Complex Inhibitors Precision Epigenetic Therapy Maximizing the Impact of Emerging Epigenetic Therapies Rational Combination of Epigenetic Agents Rational Combination with Immunotherapies Conclusions Acknowledgments Disclosures Major Papers Must Read References References Section V Targeting the B-cell Receptor (BCR) 18 The Pathologic Role of BCR Dysregulation in Lymphoid Malignancies Take Home Messages Introduction: The BCR in Normal and Malignant B Lymphocytes BCR Signaling BCR Signaling in B-cell Malignancies B-cell Proliferation in Secondary Lymphatic Organs (SLOs) The BCR Complex in Malignant B-cells CLL BCR Signaling in DLBCL Tonic BCR Signaling in Burkitt’s Lymphoma BCR Signaling in Follicular Lymphoma (FL) BCR Signaling in Mantle Cell Lymphoma (MCL) and Marginal Zone Lymphoma (MZL) Targeting BCR Signaling Bruton’s Tyrosine Kinase (BTK) Inhibitors Ibrutinib Acalabrutinib BTK Inhibitors with Anti-CD20 Antibodies Zanubrutinib Pirtobrutinib Idelalisib Conclusions Acknowledgments Conflict of Interest Must Read References References 19 Pharmacologic Features of Drugs Targeting Bruton’s Tyrosine Kinase (BTK) Take Home Messages Introduction BTK and B-cell Activating Factor Receptor (BAFFR) Signaling BTK in Cell Signaling Pathways BTK Inhibitor Development and Mechanisms of Action BTK Inhibitors in Malignancy BTK Inhibitors in Solid Cancers BTK Inhibitors in Autoimmune Diseases Mechanisms of Resistance Summary Must Read References References 20 Clinical Experience with Drugs Targeting Bruton’s Tyrosine Kinase (BTK) Take Home Messages Introduction: Chronic Lymphocytic Leukemia (CLL) Ibrutinib: Clinical Trials Ibrutinib: Real-world Evidence Acalabrutinib Ibrutinib Versus Acalabrutinib Zanubrutinib in CLL Pirtobrutinib in CLL BTK Inhibition in Indolent B-cell non-Hodgkin’s Lymphoma Mantle Cell Lymphoma (MCL) Waldenstrom’s Macroglobulinemia (WM) Marginal Zone Lymphoma (MZL) CNS Involvement with B-cell Malignancies Real-world Data Conclusions Must Read References References 21 Promising Combinations of BTK Inhibitors with Other Targeted Agents Take Home Messages Introduction Limitations of BTK Inhibitor Monotherapy Identifying Synergistic Combinations Combinations of BTK Inhibitors and Targeted Drugs as the Standard of Care BTKi + Anti-CD20 Monoclonal Antibodies Waldenstrom’s Macroglobulinemia – iNNOVATE Study Chronic Lymphocytic Leukemia (CLL) Mantle Cell Lymphoma BTKi and BCL2 Inhibitors CLL Mantle Cell Lymphoma The Future: Ongoing Clinical Trials and Additional BTKi Combinations of Interest BTKi + CDK4/6 Inhibitors BTKi + PI3Kd Inhibitors BTKi + Proteasome Inhibitors Ibrutinib + Cirmtuzumab, an Anti-ROR1 Monoclonal Antibody BTKi + mTOR Inhibitors BTKi + SYK Inhibitors BTKi + HDAC Inhibitors Ibrutinib + Selinexor Conclusions Must Read References References Section VI Protein Degraders and Membrane Transport Inhibitors 22 The Biological Basis for Targeting Protein Turnover in Malignant Cells Take Home Messages Introduction Biological Basis for Targeting Protein Turnover Approved Drugs Targeting Ubiquitin–Proteasome Pathway Pharmacologic Mechanisms of Proteasome Inhibitors Other Proteasome Inhibitors Immunomodulatory Drugs Affecting Protein Turnover Background Presently Approved Immunomodulatory Drugs Pharmacologic Mechanisms of Currently Approved Immunomodulatory Drugs Other Cereblon Modulating Agents Conclusions Acknowledgments Must Read References References 23 Preclinical Overview of Drugs Affecting Protein Turnover in Multiple Myeloma Take Home Messages Introduction Overview of Protein Handling in MM Molecular Chaperones in Protein Folding Ubiquitin–Proteasome System (UPS) Drugs Targeting the UPS Proteasome Inhibitors Inhibitors of Deubiquitinating Enzymes (DUB) Targeting Proteasome Biogenesis Molecular Glue Degraders and Proteolysis-targeting Chimera (PROTACs) Endoplasmic Reticulum (ER) Stress and the Unfolded Protein Response (UPR) Drugs Targeting the UPR Autophagy and Aggresome Pathways Targeting Nutrient Metabolism to Enhance Proteotoxic Stress The Role of Proteasome Inhibition in the Era of Immunotherapy Conclusions and Future Perspectives Must Read References References 24 Clinical Experience on Proteasome Inhibitors in Cancer Take Home Messages Introduction to Proteasome Inhibitors (Pis) Clinical Activity in Plasma Cell Disorders Role of Proteasome Inhibition in Plasma Cells: Mechanisms of Action and Mechanisms of Resistance Proteasome Inhibitors with Clinical Activity in Multiple Myeloma Bortezomib Carfilzomib Ixazomib Other Oral Proteasome Inhibitors Evaluated for Use in Patients with Multiple Myeloma Role of Proteasome Inhibitors in Amyloidosis Rationale for Combinations w/ Proteasome Inhibitors PI and Cytotoxic Agents PI + Immunomodulatory Agents (IMIDS) PI and Monoclonal Antibodies PI and HDAC Inhibitors PI and Nuclear Transport Inhibitor Selinexor Future Directions of PI-based Combination Regimens Clinical Activity of Proteasome Inhibitors in Lymphoid Malignancies Clinical Activity of Bortezomib (BTZ) in Mantle Cell Lymphoma (MCL) Bortezomib Phase 2 in R/R MCL Led to Early Approval Importing Bortezomib in the Management of MCL Clinical Activity of Bortezomib in Indolent Lymphoma (iNHL): Follicular Lymphoma, Marginal Zone, and SLL/CLL Subtypes Clinical Activity of Bortezomib in Diffuse Large B-cell Lymphoma (DLBCL) Bortezomib in Waldenstrom’s Macroglobulinemia (WM) Clinical Activity of Bortezomib in Other Lymphomas T-cell Lymphoma Hodgkin’s Lymphoma Plasmablastic Lymphoma (PBL) Lymphoblastic Lymphoma (LL)/Acute Lymphocytic Leukemia (ALL) EBV Lymphoproliferative Disorders and Other Immunological Conditions Clinical Activity of Proteasome Inhibitors in AML/MDS Clinical Activity of Proteasome Inhibitors in Solid Tumors Overcoming Resistance to Proteasome Inhibitors in Cancer and Next Steps in Proteasome Inhibition Must Read References References 25 Targeting Nuclear Protein Transport with XPO Inhibitors in Lymphoma Take Home Messages Introduction XPO1 Biology Pre-clinical and Clinical Data Phase 1 Evaluation in Non-Hodgkin’s Lymphoma DLBCL CLL T-cell Lymphoma Mantle Cell Lymphoma Toxicity Mechanisms of Intrinsic and Acquired Resistance to Selinexor and SINE Compounds Future Directions Must Read References References 26 Heterobifunctional Degraders for the Treatment of Lymphoid Malignancies Take Home Messages Biology of Protein Degraders Ubiquitin–Proteasome System and Protein Degradation Targeted Degraders in Clinical Practice Heterobifunctional Small Molecule Degraders Mechanisms of Resistance Rationale for Use of Heterobifunctional Degraders in Oncology Clinical Experience with Heterobifunctional Degraders Arvinas Phase 1/2 Trials of PR and ER Degraders ARV-110 ARV-471 Kymera Phase 1 Trial of IRAK4 Degrader KT-474 Development of Heterobifunctional Degraders in Lymphoma IRAKIMiD Degraders KT-413 BTK Degraders NX-2127 NX-5948 BGB-16673 STAT3 Degraders KT-333 Conclusions and Future Directions Must Read References References Section VII Novel Targets and Therapeutic Prospects in Development 27 Strategies for Targeting the JAK-STAT Pathway in Lymphoid Malignancies Take Home Messages JAK-STAT Signaling and Endogenous Regulators Alternative Regulation and Function of STATs Dysregulated Cytokine Signaling in Lymphoid Malignancies Strategies to Target the JAK-STAT Pathway Direct Targeting Approaches against STAT3 Oligonucleotide-based Strategies Direct STAT3 Inhibitors as Standalone Agents Natural Product Inhibitors of STAT3 Chemotherapeutic, Cytotoxic Drugs, and Other Modalities that Directly or Indirectly Inhibit STAT3 Pathway Inhibition of STAT3 Function in Combination Strategies to Sensitize Tumors and/or Reverse Resistance Clinical Trials of STAT3 Inhibitors in Lymphoid Malignancy Targeting STAT5 in Lymphoid Malignancy Clinical Trials of JAK Inhibitors in Lymphoid Malignancies Challenges and Opportunities for Clinical Application of JAK-STAT Targeting Agents Acknowledgments Conflict of Interest Disclosures Must Read References References 28 Strategies for Targeting MYC Take Home Messages Introduction Dysregulation of MYC in B-cell Lymphomas Identifying MYC Rearrangement in the Context of HGBL Targeting MYC Transcription Targeting MYC Translation Targeting MYC Stabilization and Downstream Gene Expression Initial Therapy in MYC-R DLBCL Future Directions Must Read References References 29 Targeting NOTCH in Lymphoid Malignancies Take Home Messages Introduction: NOTCH Signaling Role of NOTCH Signaling in B-cell Genetic and Microenvironmental Mechanisms of NOTCH Signaling Alteration in CLL and Lymphomas Genetic Mechanisms CLL (NOTCH1) MCL FL MZL (NOTCH2) DLBCL (N1 e N2) Other Genes of the Pathway (FBXW7, SPEN) Inhibitors Tested at the Preclinical Level Must Read References References 30 Targeting NF-κB in Oncology, an Untapped Therapeutic Potential Take Home Messages Introduction Historical Perspective for the Role of NF-κB in Malignancy Canonical NF-κB Pathway Non-canonical NF-κB Pathway NF-κB in Tumorigenesis and Promotion of Malignant Cell Growth Oncogenic Alterations in Lymphoma and Other Hematologic Malignancies Role of NF-κB in Solid Malignancies NF-κB Targeted Therapies Approved Drugs In Development Summary Must Read References References 31 Targeting the Cell Cycle and Cyclin-dependent Kinases Take Home Messages Introduction CDK Family and Cyclins CDKs Structure CDKs Activation CDKs Inhibition CDKs Function Cell Cycle-related CDK-cyclin Complexes Transcription-related CDK-cyclin Complexes DNA Damage and Repair CDK-cyclin Deregulation in Cancer Targeting CDKs in Lymphoid Malignancies CDK4/6 Inhibitors Specific Inhibitors CDK7 Inhibitors Inhibitors Targeting Multiple CDKs Resistance Future Directions Must Read References References Index EULA