Histone Deacetylase Inhibitors as Cancer Therapeutics

Contributors

Preface

Chapter One. Histone Deacetylase Inhibitors Disrupt the Mitotic Spindle Assembly Checkpoint By Targeting Histone and Nonhistone Proteins

Abbreviations

1. Introduction

2. HDACi Dysregulate Cell Cycle Progression

3. HDACi Disrupt Normal Mitosis

4. Mechanism of HDACi-Induced Aberrant Mitosis

5. Conclusions

References

Chapter Two. Mechanisms of Resistance to Histone Deacetylase Inhibitors

1. Introduction

2. Mechanisms of Resistance to HDAC Inhibitors

3. Clinical Trials of HDAC Inhibitors

4. Conclusion

References

Chapter Three. HDAC Inhibitors: Roles of DNA Damage and Repair

1. Introduction

2. HDACis and DNA Damage

3. HDACis and Oxidative Stress

4. SIRTs: DNA Damage and Oxidative Stress Responses

5. Concluding Remarks and Future Directions

References

Chapter Four. HDAC Inhibitor Modulation of Proteotoxicity as a Therapeutic Approach in Cancer

1. Background: The Cellular Response to Proteotoxicity

2. Proteotoxicity as a Therapeutic Target in Cancer

3. Summary and Future Directions

References

Chapter Five. Intrinsic and Extrinsic Apoptotic Pathway Signaling as Determinants of Histone Deacetylase Inhibitor Antitumor Activity

1. Introduction

2. The Intrinsic Apoptosis Pathway

3. HDACi Induce Apoptosis Via the Intrinsic Apoptosis Pathway

4. The Effects of HDACi on Antiapoptotic Bcl-2 Family Genes

5. Effects of HDACi on Proapoptotic BCL-2 Family Members

6. Effects of HDACi on Bid

7. Effects of HDACi on Bim

8. Effects of HDACi on Bmf

9. Effects of HDACi on Bad

10. Effects of HDACi on Noxa/Puma

11. Effects of HDACi on Bax and/or Bak

12. The Extrinsic Apoptosis Pathway

13. Effects of HDACi on the Extrinsic Apoptosis Pathway

14. Effects of HDACi on DR and Their Ligands

15. Concluding Remarks

References

Chapter Six. Histone Deacetylase Inhibitors and Rational Combination Therapies

Abbreviations

1. Introduction

2. Histone Deacetylases

3. Histone Deacetylase Inhibitors

4. Determinants of HDAC Inhibitor Lethality

5. HDACI Strategies in Cancer Therapy

6. Summary and Future Directions

References

Chapter Seven. HDAC Inhibitors and Chaperone Function

1. Introduction

2. HDAC Inhibitors

3. Chaperones and Protein Homeostasis

4. Regulation of Hsp90 Chaperone Function by Reversible Acetylation

5. HDAC3 is the Nuclear Hsp90 Deacetylase

6. HDAC Inhibitor-Mediated Regulation of Hsp70

7. HDAC Regulation of Hsp40

8. Regulation of GRP78 Function by HDAC6

9. Concluding Remarks

References

Index