BOOK
The Treatment of Myeloid Malignancies with Kinase Inhibitors, An Issue of Hematology/Oncology Clinics of North America, E-Book
(2017)
Additional Information
Book Details
Abstract
This issue of Hematology/Oncology Clinics will focus on The Treatment of Myeloid Malignancies with Kinase Inhibitors. Articles will focus on: Targeting aberrant signaling in myeloid malignancies: promise versus reality; The development and use of imatinib for the treatment of chronic myelogenous leukemia; Mechanisms of resistance to ABL kinase inhibition in CML and the development of next generation ABL kinase inhibitors; Tyrosine kinase inhibitors in the treatment of systemic mastocytosis and hypereosinophilic syndrome; The development and use of JAK2 inhibitors for the treatment of myeloproliferative neoplasms (MPN); Mechanisms of resistance to JAK2 inhibitors in MPN; Kinase inhibitor screening in myeloid malignancies; and more!
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| The Treatment of Myeloid Malignancies with Kinase Inhibitors\r | i | ||
| Copyright\r | ii | ||
| Contributors | iii | ||
| CONSULTING EDITORS | iii | ||
| EDITOR | iii | ||
| AUTHORS | iii | ||
| Contents | v | ||
| Preface: Kinase Inhibitors in the Treatment of Myeloid Malignancies | v | ||
| Targeting Aberrant Signaling in Myeloid Malignancies: Promise Versus Reality | v | ||
| Tyrosine Kinase Inhibitor Treatment for Newly Diagnosed Chronic Myeloid Leukemia | v | ||
| Mechanisms of Resistance to ABL Kinase Inhibition in Chronic Myeloid Leukemia and the Development of Next Generation ABL Ki ... | v | ||
| The Development and Use of Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms | vi | ||
| Mechanisms of Resistance to JAK2 Inhibitors in Myeloproliferative Neoplasms | vi | ||
| Tyrosine Kinase Inhibitors in the Treatment of Eosinophilic Neoplasms and Systemic Mastocytosis | vi | ||
| The Development of FLT3 Inhibitors in Acute Myeloid Leukemia | vi | ||
| Mechanisms of Resistance to FLT3 Inhibitors and the Role of the Bone Marrow Microenvironment | vii | ||
| Kinase Inhibitor Screening in Myeloid Malignancies | vii | ||
| Identification and Targeting of Kinase Alterations in Histiocytic Neoplasms | vii | ||
| HEMATOLOGY/ONCOLOGY\rCLINICS OF NORTH AMERICA\r\r | viii | ||
| FORTHCOMING ISSUES | viii | ||
| October 2017 | viii | ||
| December 2017 | viii | ||
| February 2018 | viii | ||
| RECENT ISSUES | viii | ||
| June 2017 | viii | ||
| April 2017 | viii | ||
| February 2017 | viii | ||
| Preface:\rKinase Inhibitors in the Treatment of Myeloid Malignancies | ix | ||
| Targeting Aberrant Signaling in Myeloid Malignancies | 565 | ||
| Key points | 565 | ||
| INTRODUCTION | 565 | ||
| WHAT MAKES A GOOD DRUG-TARGET PAIRING? | 567 | ||
| DRUGGING THE UNDRUGGABLE | 567 | ||
| ONCOGENE ADDICTION VERSUS DISEASE ACCELERATION | 568 | ||
| ON-TARGET TOXICITY AS A THERAPEUTIC LIABILITY | 570 | ||
| WHERE DO WE GO FROM HERE? | 571 | ||
| SUMMARY | 572 | ||
| REFERENCES | 573 | ||
| Tyrosine Kinase Inhibitor Treatment for Newly Diagnosed Chronic Myeloid Leukemia | 577 | ||
| Key points | 577 | ||
| INTRODUCTION: A SHORT HISTORY OF THE DEVELOPMENT OF TYROSINE KINASE INHIBITOR THERAPY | 577 | ||
| HOW TO DIAGNOSE CHRONIC MYELOID LEUKEMIA | 579 | ||
| CLINICAL AND PATHOLOGIC STAGING OF CHRONIC MYELOID LEUKEMIA | 579 | ||
| OUTCOME MEASURES WITH TYROSINE KINASE INHIBITOR TREATMENT OF CHRONIC MYELOID LEUKEMIA | 579 | ||
| MONITORING OF TREATMENT RESPONSE | 580 | ||
| INITIAL TYROSINE KINASE INHIBITOR THERAPY FOR CHRONIC PHASE CHRONIC MYELOID LEUKEMIA | 581 | ||
| CLINICALLY RELEVANT RESPONSE MILESTONES IN CHRONIC MYELOID LEUKEMIA TREATMENT | 581 | ||
| MUTATIONAL ANALYSIS FOR RESISTANCE/RELAPSE | 582 | ||
| SWITCHING TO A DIFFERENT TYROSINE KINASE INHIBITOR FOR RESISTANCE | 582 | ||
| TYROSINE KINASE INHIBITOR TOXICITY AND WHAT TO DO ABOUT IT | 583 | ||
| DISCONTINUATION OF TYROSINE KINASE INHIBITOR AFTER PROLONGED “DEEP” MOLECULAR RESPONSE | 584 | ||
| SUMMARY | 585 | ||
| REFERENCES | 585 | ||
| Mechanisms of Resistance to ABL Kinase Inhibition in Chronic Myeloid Leukemia and the Development of Next Generation ABL Ki ... | 589 | ||
| Key points | 589 | ||
| INTRODUCTION | 590 | ||
| DEFINITIONS | 590 | ||
| BCR-ABL1–Dependent Resistance | 591 | ||
| BCR-ABL1 kinase domain mutations | 591 | ||
| General considerations | 591 | ||
| Clinically observed BCR-ABL1 kinase domain mutations and structure–function relationships | 592 | ||
| Increased BCR-ABL1 expression | 594 | ||
| Drug influx/efflux pumps | 596 | ||
| Organic-cation transporter-1 | 596 | ||
| Tyrosine kinase inhibitor bioavailability | 596 | ||
| BCR-ABL1–Independent Resistance | 596 | ||
| General considerations | 596 | ||
| STAT3 | 597 | ||
| PI3K/AKT | 597 | ||
| RAF/MEK/ERK | 597 | ||
| Nucleocytoplasmic transport | 600 | ||
| EZH2 | 600 | ||
| New Therapies | 600 | ||
| Tyrosine kinase inhibitors | 600 | ||
| ABL001 | 600 | ||
| Drug combinations to eradicate leukemic stem cells and eliminate minimal residual disease | 601 | ||
| Tyrosine kinase inhibitors plus immune therapies | 604 | ||
| Tyrosine kinase inhibitors plus inhibitors of additional pathways | 604 | ||
| SUMMARY | 605 | ||
| REFERENCES | 605 | ||
| The Development and Use of Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms | 613 | ||
| Key points | 613 | ||
| INTRODUCTION | 614 | ||
| PRECLINICAL DEVELOPMENT OF JANUS KINASE INHIBITORS | 615 | ||
| CLINICAL DEVELOPMENT OF JANUS KINASE INHIBITORS | 616 | ||
| Ruxolitinib for Myelofibrosis | 616 | ||
| Ruxolitinib for Polycythemia Vera | 617 | ||
| Pacritinib | 618 | ||
| Momelotinib | 620 | ||
| NS-018 | 621 | ||
| INCB-39100 | 621 | ||
| JAK2V617F INHIBITORS | 621 | ||
| Targeting Janus Kinase-2 in the Inactive State | 622 | ||
| Targeting the Adenosine Triphosphate Binding Site in the Janus Kinase-2 Pseudokinase Domain | 622 | ||
| Targeting Allosteric Sites Specifically Involved in JAK2V617F Activation | 622 | ||
| Summary | 622 | ||
| ACKNOWLEDGMENTS | 623 | ||
| REFERENCES | 623 | ||
| Mechanisms of Resistance to JAK2 Inhibitors in Myeloproliferative Neoplasms | 627 | ||
| Key points | 627 | ||
| INTRODUCTION | 627 | ||
| RESISTANCE TO JAK2 INHIBITORS | 629 | ||
| Molecular Mechanisms of JAK2 Inhibitor Resistance | 629 | ||
| Genetic resistance | 629 | ||
| Functional resistance by persistence of JAK-STAT signaling | 632 | ||
| Functional resistance by protective cytokine effects | 633 | ||
| Intrinsic resistance in myelofibrosis | 633 | ||
| Clinical Aspects of JAK2 Inhibitor Resistance | 633 | ||
| APPROACHES TO OVERCOME RESISTANCE TO JAK2 INHIBITORS IN MYELOPROLIFERATIVE NEOPLASMS | 634 | ||
| Type I JAK2 Inhibitors | 634 | ||
| Heat Shock Protein 90 Inhibition | 636 | ||
| Type II JAK2 Inhibition | 636 | ||
| Combination Therapy Approaches | 637 | ||
| PI3K/Akt/Mammalian Target of Rapamycin Pathway | 637 | ||
| PIM Kinases | 637 | ||
| Bcl-2/Bcl-xL Inhibition | 637 | ||
| Pan-Histone Deacetylase Inhibitors | 638 | ||
| Additional Novel Concepts | 638 | ||
| REFERENCES | 638 | ||
| Tyrosine Kinase Inhibitors in the Treatment of Eosinophilic Neoplasms and Systemic Mastocytosis | 643 | ||
| Key points | 643 | ||
| INTRODUCTION | 643 | ||
| EOSINOPHILIC NEOPLASMS | 644 | ||
| Imatinib in Patients with PDGFRA/B Fusion Genes | 644 | ||
| FGFR1 Fusion Genes | 647 | ||
| Targeting the Janus Kinase/Signal Transducers and Activators of Transcription Pathway in Eosinophilic Neoplasms | 649 | ||
| FMS-like Tyrosine Kinase 3 Fusion Genes | 649 | ||
| SYSTEMIC MASTOCYTOSIS | 650 | ||
| Dasatinib and Nilotinib | 650 | ||
| Imatinib | 650 | ||
| Masitinib | 651 | ||
| Midostaurin | 651 | ||
| BLU-285 | 654 | ||
| Targeting the Janus Kinase/Signal Transducers and Activators of Transcription Pathway in Systemic Mastocytosis | 654 | ||
| SUMMARY | 655 | ||
| REFERENCES | 655 | ||
| The Development of FLT3 Inhibitors in Acute Myeloid Leukemia | 663 | ||
| Key points | 663 | ||
| INTRODUCTION | 663 | ||
| FLT3 PATHWAY ACTIVATION IN ACUTE MYELOID LEUKEMIA | 664 | ||
| IMPACT OF FLT3 MUTATIONS ON PROGNOSIS | 664 | ||
| CHALLENGES TO TARGETING FLT3 | 664 | ||
| CLINICAL EVALUATION OF FLT3 INHIBITORS | 665 | ||
| FLT3 INHIBITORS | 665 | ||
| First-Generation FLT3 Inhibitors | 665 | ||
| Lestaurtinib | 665 | ||
| Midostaurin | 665 | ||
| Sunitinib | 670 | ||
| Sorafenib | 670 | ||
| Second-Generation FLT3 Inhibitors | 671 | ||
| Quizartinib | 671 | ||
| Crenolanib | 671 | ||
| Gilteritinib | 672 | ||
| Summary of monotherapy with FLT3 inhibitors in acute myeloid leukemia | 672 | ||
| RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA STUDIES WITH FLT3 INHIBITORS COMBINED WITH STANDARD THERAPIES | 672 | ||
| First-Generation FLT3 Inhibitors in Combination with Conventional Salvage Chemotherapy | 672 | ||
| Lestaurtinib | 672 | ||
| Sunitinib | 673 | ||
| Second-Generation FLT3 Inhibitors in Combination with Conventional Salvage Chemotherapy | 673 | ||
| TREATMENT-NAIVE ACUTE MYELOID LEUKEMIA STUDIES WITH FLT3 INHIBITORS IN COMBINATION WITH CONVENTIONAL CHEMOTHERAPY | 673 | ||
| Lestaurtinib | 673 | ||
| Sorafenib | 673 | ||
| Quizartinib | 674 | ||
| Midostaurin | 674 | ||
| Crenolanib | 674 | ||
| FLT3 INHIBITORS IN COMBINATION WITH HYPOMETHYLATING AGENTS | 675 | ||
| Summary of FLT3 Inhibitors in Combination with Standard Chemotherapy | 675 | ||
| ROLE FOR FLT3 INHIBITION AS MAINTENANCE THERAPY | 675 | ||
| SUMMARY | 676 | ||
| REFERENCES | 676 | ||
| Mechanisms of Resistance to FLT3 Inhibitors and the Role of the Bone Marrow Microenvironment | 681 | ||
| Key points | 681 | ||
| INTRODUCTION | 681 | ||
| ACUTE MYELOID LEUKEMIA CELLS DURING TREATMENT WITH FLT3 INHIBITORS | 682 | ||
| Bypassing the FLT3 Receptor | 683 | ||
| Suboptimal Pharmacokinetics and Pharmacodynamics | 683 | ||
| EMERGENCE OF RESISTANCE | 685 | ||
| Mutations in the Target Receptor | 685 | ||
| Activation of Alternative Signaling Pathways | 685 | ||
| STRATEGIES TO PREVENT THE DEVELOPMENT OF RESISTANCE OR TO SENSITIZE CELLS TO FLT3 INHIBITORS | 687 | ||
| TANDEM DUPLICATION ACUTE MYELOID LEUKEMIA | 688 | ||
| REFERENCES | 688 | ||
| Kinase Inhibitor Screening in Myeloid Malignancies | 693 | ||
| Key points | 693 | ||
| INTRODUCTION | 693 | ||
| KINASES AS GENE TARGETS IN MYELOID MALIGNANCY | 693 | ||
| Chromosomal Translocation | 694 | ||
| Point Mutations and Insertion/Deletions | 694 | ||
| Aberrant Expression | 694 | ||
| Oncorequisite Pathways | 694 | ||
| Microenvironment | 695 | ||
| FUNCTIONAL SCREENING AS A TOOL TO UNDERSTAND KINASE PATHWAY DYSREGULATION | 695 | ||
| Kinase Inhibitor Screening to Identify Pathway Dependence in Individual Patients | 695 | ||
| Cohort-Based Kinase Inhibitor Screening | 696 | ||
| Common Pathways/Drugs for Disease Subsets | 696 | ||
| Drug Repurposing | 697 | ||
| Kinase Inhibitor Screening to Refine Diagnostic and Therapeutic Markers | 697 | ||
| Application of Functional Kinase Inhibitor Screening in Lymphoid Malignancies | 698 | ||
| Drug Combinations | 698 | ||
| Beyond Kinase Inhibitors | 699 | ||
| SUMMARY | 699 | ||
| REFERENCES | 699 | ||
| Identification and Targeting of Kinase Alterations in Histiocytic Neoplasms | 705 | ||
| Key points | 705 | ||
| INTRODUCTION | 705 | ||
| SYSTEMIC HISTIOCYTIC NEOPLASMS AND THEIR CURRENT CLASSIFICATION | 706 | ||
| PROTOONCOGENE MUTATIONS IN HISTIOCYTOSES | 706 | ||
| DISCOVERY OF ADDITIONAL KINASE ALTERATIONS IN HISTIOCYTOSES | 708 | ||
| A-RAF Protooncogene | 708 | ||
| Mitogen-Activated Protein Kinase Kinase 1 | 708 | ||
| Ras Isoforms | 708 | ||
| Phosphoinositide 3-Kinases Isoforms | 709 | ||
| Mitogen-Activated Protein Kinase Kinase Kinase 1 | 709 | ||
| GENE FUSIONS | 709 | ||
| THERAPEUTIC EFFICACY OF KINASE INHIBITOR THERAPY IN HISTIOCYTOSES | 710 | ||
| RAF Inhibitors | 711 | ||
| MEK Inhibitors | 714 | ||
| Mammalian Target of Rapamycin Inhibitors | 715 | ||
| SUMMARY | 715 | ||
| REFERENCES | 716 |