BOOK
New Drugs for Malignancy, An Issue of Hematology/Oncology Clinics of North America - E-Book
(2012)
Additional Information
Book Details
Abstract
Topics include: Targeting IGF-1R, Tyrosine Kinase Inhibitors in Lung Cancer, Targeting mTOR, Targeting Hedgehog, Mitotic Inhibitors, Topoisomerase I Inhibitors , and New Strategies and Drugs Inhibiting Folate Pathways.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Hematology/Oncology Clinics of North America | i | ||
| Copyright Page | ii | ||
| Table of Contents | vii | ||
| Contributors | iii | ||
| Preface: Clinical Drug Development in 2012 | xi | ||
| Chapter 1. Therapeutic Antibodies Against Cancer | 447 | ||
| mAbs APPROVED FOR CLINICAL USE | 450 | ||
| mAbs IN CLINICAL AND PRECLINICAL DEVELOPMENT | 461 | ||
| SAFETY, EFFICACY, AND QUALITY OF CANDIDATE THERAPEUTIC mAbs | 462 | ||
| BIOSIMILAR AND BIOBETTER THERAPEUTIC ANTIBODIES | 467 | ||
| SUMMARY | 467 | ||
| ACKNOWLEDGMENTS | 468 | ||
| REFERENCES | 468 | ||
| Chapter 2. mTOR Signaling Pathway and mTOR Inhibitors in Cancer Therapy | 483 | ||
| mTOR PATHWAY AND FUNCTION | 483 | ||
| UPSTREAM REGULATORS OF mTOR | 485 | ||
| NEGATIVE REGULATORS | 486 | ||
| NEGATIVE FEEDBACK AND POSITIVE FEED-FORWARD LOOPS | 486 | ||
| CROSSTALK | 487 | ||
| mTOR IN CANCER | 487 | ||
| mTOR PATHWAY INHIBITORS IN CANCER | 489 | ||
| mTOR INHIBITORS APPROVED BY FDA FOR TREATMENT OF CANCER | 489 | ||
| mTOR INHIBITORS IN OTHER MALIGNANCIES | 492 | ||
| NEW STRATEGIES TO IMPLEMENT THE EFFECT OF mTOR INHIBITORS IN CANCER | 496 | ||
| REFERENCES | 497 | ||
| Chapter 3. Topoisomerase 1 Inhibitors and Cancer Therapy | 507 | ||
| IRINOTECAN | 509 | ||
| TOPOTECAN | 511 | ||
| CURRENT QUESTIONS AND FUTURE DIRECTIONS | 513 | ||
| NON-CPT TOP1 INHIBITORS | 519 | ||
| SUMMARY | 519 | ||
| REFERENCES | 520 | ||
| Chapter 4. Targeting the Insulin Growth Factor Receptor 1 | 527 | ||
| IGF AXIS IN CANCER | 530 | ||
| TARGETING IGF1R | 531 | ||
| CHALLENGES AND FUTURE DIRECTIONS | 535 | ||
| REFERENCES | 535 | ||
| Chapter 5. Targeting Angiogenesis in Gynecologic Cancers | 543 | ||
| ANGIOGENESIS | 544 | ||
| BEVACIZUMAB | 544 | ||
| VEGF TRAP (AFLIBERCEPT) | 549 | ||
| SMALL MOLECULE TYROSINE KINASE INHIBITORS | 549 | ||
| EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODIES AND TYROSINE KINASE INHIBITORS | 551 | ||
| ALTERNATIVE TARGETS AND STRATEGIES | 554 | ||
| SUMMARY | 556 | ||
| REFERENCES | 557 | ||
| Chapter 6. Targeting the Hedgehog Pathway: Role in Cancer and Clinical Implications of Its Inhibition | 565 | ||
| PATHWAY SIGNAL TRANSDUCTION | 566 | ||
| LINKING THE Hh PATHWAY AND HUMAN CANCER | 568 | ||
| MODELS OF PATHWAY ACTIVATION IN CANCER | 568 | ||
| DISCOVERY OF THE FIRST HH INHIBITOR: CYCLOPAMINE | 570 | ||
| HH PATHWAY INHIBITORS | 570 | ||
| LIGAND-INDEPENDENT TUMORS AND HH INHIBITION | 575 | ||
| LIGAND-DEPENDENT TUMORS AND Hh INHIBITION | 578 | ||
| ONGOING CLINICAL TRIALS | 581 | ||
| CHALLENGES TARGETING THE HH PATHWAY | 581 | ||
| SUMMARY | 582 | ||
| REFERENCES | 582 | ||
| Chapter 7. Tyrosine Kinase Inhibitors in Lung Cancer | 589 | ||
| EPIDERMAL GROWTH FACTOR RECEPTOR TYROSINE KINASE INHIBITORS | 590 | ||
| ANAPLASTIC LYMPHOMA KINASE TYROSINE KINASE INHIBITORS | 595 | ||
| MET/HEPATOCYTE GROWTH FACTOR INHIBITORS | 597 | ||
| VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR TYROSINE KINASE INHIBITORS | 599 | ||
| SUMMARY | 599 | ||
| REFERENCES | 599 | ||
| Chapter 8. Antimitotic Inhibitors | 607 | ||
| MICROTUBULE STRUCTURE | 608 | ||
| MICROTUBULE-TARGETING AGENTS | 608 | ||
| LIMITATIONS IN THE CLINICAL USE OF MICROTUBULE-TARGETING AGENTS | 609 | ||
| EPOTHILONE B ANALOGUE: SAGOPILONE (ZK-EPO) | 614 | ||
| EPOTHILONE D ANALOGUES: KOS-862 AND KOS-1584 | 614 | ||
| HALICHONDRIN B ANALOGUE: ERIBULIN MESYLATE | 615 | ||
| SUMMARY | 619 | ||
| REFERENCES | 620 | ||
| Chapter 9. The Antifolates | 629 | ||
| ANTIFOLATES ACHIEVE THEIR PHARMACOLOGIC EFFECTS BY THEIR PERTURBATIONS OF FOLATE METABOLISM | 630 | ||
| PHARMACOLOGIC CONSEQUENCES OF THE FORMATION OF METHOTREXATE POLYGLUTAMATE DERIVATIVES WITHIN CELLS | 634 | ||
| THE MEMBRANE TRANSPORT OF ANTIFOLATES MEDIATED BY FACILITATIVE CARRIERS AND EXPORT PUMPS | 635 | ||
| HIGH-DOSE MTX WITH LEUCOVORIN RESCUE | 637 | ||
| CURRENT CLINICAL APPLICATIONS OF METHOTREXATE | 638 | ||
| THE EMERGENCE OF A NEW-GENERATION 4-AMINO-ANTIFOLATE: PRALATREXATE | 638 | ||
| THE EMERGENCE OF ANTIFOLATES THAT TARGET TETRAHYDROFOLATE-REQUIRING ENZYMES | 638 | ||
| THE IMPACT OF PHYSIOLOGIC FOLATES ON THE ANTITUMOR ACTIVITIES AND TOXICITY OF ANTIFOLATES | 639 | ||
| MECHANISMS OF RESISTANCE TO ANTIFOLATES | 640 | ||
| TARGETING DRUGS TO TUMOR CELLS VIA FOLATE TRANSPORTERS | 640 | ||
| REFERENCES | 642 | ||
| Chapter 10. Poly(Adenosine Diphosphate – Ribose) Polymerase Inhibitors in Cancer Treatment | 649 | ||
| DNA DAMAGE AND REPAIR MECHANISMS | 650 | ||
| DNA REPAIR SYNTHETIC LETHALITY AS A THERAPEUTIC TARGET | 651 | ||
| PARP INHIBITORS | 654 | ||
| MONOTHERAPY WITH PARP INHIBITORS IN BRCA-MUTANT CANCERS | 656 | ||
| MONOTHERAPY WITH PARP INHIBITORS IN SPORADIC CANCERS | 657 | ||
| COMBINATION OF PARP INHIBITORS WITH CHEMOTHERAPY | 658 | ||
| BIOMARKERS FOR EFFICACY OF PARP INHIBITORS | 661 | ||
| SUMMARY | 665 | ||
| REFERENCES | 665 | ||
| Chapter 11. Role of Histone Deacetylase Inhibitors in the Treatment of Lymphomas and Multiple Myeloma | 671 | ||
| BIOLOGY OF HDACs | 672 | ||
| BIOLOGY OF HDACI | 672 | ||
| RATIONALE FOR ACTIVITY IN LYMPHOID MALIGNANCIES | 673 | ||
| PHARMACOLOGY OF HDACI | 683 | ||
| HDACI IN LYMPHOMA (CLINICAL DATA) | 686 | ||
| SUMMARY | 694 | ||
| REFERENCES | 695 | ||
| Index | 705 |