Tumor Suppressing Viruses, Genes, and Drugs: Innovative Cancer Therapy Approaches (Hardcover)

Contributors

Preface

1 Oncolytic Viruses: Virotherapy for Cancer

I. Introduction

II. Attributes of Replication-Selective Viruses for Cancer Treatment

III. Approaches to Optimizing Tumor-Selective Viral Replication

IV. Adenoviruses

V. Poliovirus

VI. Vesicular Stomatitis Virus

VII. Reovirus

VIII. Bacteria

IX. Vaccinia Virus

X. Herpesvirus

XI. Clinical Trial Results with Replication-Competent Adenoviruses in Cancer Patients

XII. Results from Clinical Trials with dl1520 (Onyx-015, or CI-1042)

XIII. Future Directions: Approaches to Improving the Efficacy of Replication-Selective Viral Agents

XIV. Summary

References

2 Reovirus Therapy of Ras-Associated Cancers

I. Introduction

II. Reovirus Oncolysis

III. Concluding Remarks

References

3 Oncolytic Herpes Simplex Virus (G207) Therapy: From Basic to Clinical

I. Introduction

II. Preclinical Studies of G207

III. G207 Clinical Trial

IV. Conclusions

References

4 p53 and Its Targets

I. Introduction

II. Activation of p53

III. Downstream Mediators of p53

References

5 Prospects for Tumor Suppressor Gene Therapy: RB as an Example

I. Introduction

II. Functions of RB

III. Successes with RB Gene Therapy

IV. Perspectives

References

6 CDK Inhibitors: Genes and Drugs

I. Introduction

II. G1 Regulation

III. p16INK4a and the Rb Pathway

IV. p19ARF and p53 Pathway

V. p27 and Human Cancer

VI. Conclusions and Future Perspectives

References

7 CDK Inhibitors: Small Molecular Weight Compounds

I. Introduction

II. Cyclin-Dependent Kinases, the Cell Cycle, and Cancer

III. Cyclin-Dependent Kinase Inhibitors, a Large Variety of Structures

IV. Cyclin-Dependent Kinase Inhibitors, All Competing with ATP

V. Cyclin-Dependent Kinase Inhibitors, the Selectivity Problem

VI. Cyclin-Dependent Kinase Inhibitors, Cellular Effects

VII. Cyclin-Dependent Kinase Inhibitors, Antitumor Activity

VIII. Conclusion

References

8 NF1 and Other RAS-Binding Peptides

I. RAS Molecules: Normal versus Oncogenic Mutants

II. Super GAP?

III. RAS-Binding Fragment of NF1

IV. c-RAF-1

V. PI-3 Kinase

VI. Ral GDS

References

9 Cytoskeletal Tumor Suppressor Genes

I. Introduction (Historical Background)

II. Type I Cytoskeletal Tumor Suppressors

III. Type II Cytoskeletal Tumor Suppressors

References

10 TGF-? Signaling and Carcinogenesis

I. Introduction

II. Dual Role of TGF-? in Carcinogenesis

III. TGF-? Superfamily Signaling

IV. Perturbation of TGF-? Signaling in Cancer Cells

V. Perspectives

References

11 DAN Gene

I. Introduction

II. Cloning of DAN cDNA

III. Transfection of DAN

IV. Role of DAN in Neuroblastomas

V. Structural Features of the DAN Protein

VI. Genomic Structure of DAN

VII. DAN Family

References

12 Design of Hammerhead Ribozymes and Allosterically Controllable Maxizymes for Cancer Gene Therapy

I. Introduction

II. Ribozyme Expression System in Cells

III. Design of the tRNAVal-Driven Ribozyme That Is Transcribed by pol III

IV. Design of Allosterically Controlled Maxizymes

V. Conclusion

References

13 Inhibitors of Angiogenesis

I. Introduction?Angiogenesis

II. Angiogenesis Inhibitors

III. Future Directions

References

14 Geranylgeranylated RhoB Mediates the Apoptotic and Antineoplastic Effects of Farnesyltransferase Inhibitors: New Insights into Cancer Cell Suicide

I. Introduction

II. Do Farnesyltransferase Inhibitors Target a Unique Aspect of Neoplastic Pathophysiology?

III. Ras Is Not a Crucial Target of Farnesyltransferase Inhibitors

IV. RhoB Is a Crucial Target of Farnesyltransferase Inhibitors

V. Farnesyltransferase Inhibitors Act through a Gain of Function Mechanism Involving RhoB-GG

VI. RhoB-GG Is Required to Mediate Apoptosis by Farnesyltransferase Inhibitors

VII. RhoB-GG and the Antiangiogenic Properties of Farnesyltransferase Inhibitors

VIII. Clinical Implications

IX. Summary

References

15 RAS Binding Compounds

I. Introduction

II. Ras Cycle and Ras?Raf Signaling Pathway

III. The Structure of Ras Proteins

IV. Drug Target Sites of Ras

V. Conclusions and Outlook

References

16 Actin-Binding Drugs: MKT-077 and Chaetoglobosin K (CK)

I. Introduction

II. MKT-077: F-Actin Bundler

III. Chaetoglobosin K: F-Actin Capper

References

17 Tyr Kinase Inhibitors as Potential Anticancer Agents: EGF Receptor and ABL Kinases

I. Introduction

II. Tyr Kinase Inhibitors

III. Chronic Myelogenous Leukemia

IV. Epidermal Growth Factor Receptor

V. Antagonists of the Epidermal Growth Factor Receptor Extracellular Domain

VI. Chemical Inhibitors of the Kinase Domain of the Epidermal Growth Factor Receptor

VII. Epidermal Growth Factor Receptor Antagonists or Inhibitors Act Synergistically to Kill Tumor Cells

VIII. The Effects of Abl Inhibitors on Leukemia

References

18 Antagonists of Rho Family GTPases: Blocking PAKs, ACKs, and Rock

I. Rho Family GTPases (Rho, Rac, and CDC42)

II. Blocking PAKs

III. Blocking CDC42 Pathways (ACKs and N-WASP)

IV. Blocking Rho Pathways

V. Rac-Specific Inhibitors?

References

19 Integrin Antagonists as Cancer Therapeutics

I. Introduction

II. Signaling Pathways Activated by Integrins

InII. Role of Integrins in Neoplastic Transformatio

IV. Role of Integrins in Tumor-Induced Angiogenesis

V. Integrin Antagonists as Antiangiogenesis Agents

VI. Conclusions and Future Perspectives

References

20 Functional Rescue of Mutant p53 as a Strategy to Combat Cancer

I. Introduction

II. Multiple Pathways of p53-Induced Apoptosis

III. Regulation of p53 Activity

IV. Approaches toward Reactivation of Mutant p53

V. Implications for Tumor Therapy and Future Perspectives

References

Index