Tumor Suppressing Viruses, Genes, and Drugs: Innovative Cancer Therapy Approaches
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Table of contents
- Cover
- Contentsv
- Contributorsxi
- Prefacexv
- Chapter 1. Oncolytic Viruses: Virotherapy for Cancer1
- I. Introduction2
- II. Attributes of Replication-Selective Viruses for Cancer Treatment4
- III. Approaches to Optimizing Tumor-Selective Viral Replication4
- IV. Adenoviruses5
- V. Poliovirus7
- VI. Vesicular Stomatitis Virus8
- VII. Reovirus8
- VIII. Bacteria9
- IX. Vaccinia Virus10
- X. Herpesvirus12
- XI. Clinical Trial Results with Replication-Competent Adenoviruses in Cancer Patients16
- XII. Results from Clinical Trials with dl1520 (Onyx-015, or CI-1042)19
- XIII. Future Directions: Approaches to Improving the Efficacy of Replication-Selective Viral Agents23
- XIV. Summary24
- References24
- Chapter 2. Reovirus Therapy of Ras-Associated Cancers31
- I. Introduction31
- II. Reovirus Oncolysis34
- III. Concluding Remarks40
- References41
- Chapter 3. Oncolytic Herpes Simplex Virus (G207) Therapy: From Basic to Clinical45
- I. Introduction45
- II. Preclinical Studies of G20748
- III. G207 Clinical Trial65
- IV. Conclusions67
- References68
- Chapter 4. p53 and Its Targets77
- I. Introduction77
- II. Activation of p5378
- III. Downstream Mediators of p5381
- References90
- Chapter 5. Prospects for Tumor Suppressor Gene Therapy: RB as an Example97
- I. Introduction97
- II. Functions of RB100
- III. Successes with RB Gene Therapy110
- IV. Perspectives113
- References115
- Chapter 6. CDK Inhibitors: Genes and Drugs123
- I. Introduction123
- II. G1 Regulation124
- III. p16INK4a and the Rb Pathway131
- IV. p19ARF and p53 Pathway133
- V. p27 and Human Cancer135
- VI. Conclusions and Future Perspectives136
- References137
- Chapter 7. CDK Inhibitors: Small Molecular Weight Compounds145
- I. Introduction145
- II. Cyclin-Dependent Kinases, the Cell Cycle, and Cancer146
- III. Cyclin-Dependent Kinase Inhibitors, a Large Variety of Structures149
- IV. Cyclin-Dependent Kinase Inhibitors, All Competing with ATP151
- V. Cyclin-Dependent Kinase Inhibitors, the Selectivity Problem152
- VI. Cyclin-Dependent Kinase Inhibitors, Cellular Effects154
- VII. Cyclin-Dependent Kinase Inhibitors, Antitumor Activity155
- VIII. Conclusion161
- References162
- Chapter 8. NF1 and Other RAS-Binding Peptides169
- I. RAS Molecules: Normal versus Oncogenic Mutants169
- II. Super GAP?170
- III. RAS-Binding Fragment of NF1171
- IV. c-RAF-1172
- V. PI-3 Kinase173
- VI. Ral GDS173
- References174
- Chapter 9. Cytoskeletal Tumor Suppressor Genes177
- I. Introduction (Historical Background)177
- II. Type I Cytoskeletal Tumor Suppressors179
- III. Type II Cytoskeletal Tumor Suppressors186
- References192
- Chapter 10. TGF-β Signaling and Carcinogenesis199
- I. Introduction199
- II. Dual Role of TGF-β in Carcinogenesis200
- III. TGF-β Superfamily Signaling200
- IV. Perturbation of TGF-β Signaling in Cancer Cells207
- V. Perspectives212
- References213
- Chapter 11. DAN Gene221
- I. Introduction221
- II. Cloning of DAN cDNA222
- III. Transfection of DAN223
- IV. Role of DAN in Neuroblastomas223
- V. Structural Features of the DAN Protein225
- VI. Genomic Structure of DAN228
- VII. DAN Family228
- References231
- Chapter 12. Design of Hammerhead Ribozymes and Allosterically Controllable Maxizymes for Cancer Gene233
- I. Introduction233
- II. Ribozyme Expression System in Cells236
- III. Design of the tRNAVal-Driven Ribozyme That Is Transcribed by pol III240
- IV. Design of Allosterically Controlled Maxizymes246
- V. Conclusion255
- References256
- Chapter 13. Inhibitors of Angiogenesis261
- I. Introduction„Angiogenesis261
- II. Angiogenesis Inhibitors265
- III. Future Directions274
- References276
- Chapter 14. Geranylgeranylated RhoB Mediates the Apoptotic and Antineoplastic Effects of Farnesyltra293
- I. Introduction293
- II. Do Farnesyltransferase Inhibitors Target a Unique Aspect of Neoplastic Pathophysiology?294
- III. Ras Is Not a Crucial Target of Farnesyltransferase Inhibitors294
- IV. RhoB Is a Crucial Target of Farnesyltransferase Inhibitors295
- V. Farnesyltransferase Inhibitors Act through a Gain of Function Mechanism Involving RhoB-GG297
- VI. RhoB-GG Is Required to Mediate Apoptosis by Farnesyltransferase Inhibitors298
- VII. RhoB-GG and the Antiangiogenic Properties of Farnesyltransferase Inhibitors302
- VIII. Clinical Implications302
- IX. Summary304
- References305
- Chapter 15. RAS Binding Compounds311
- I. Introduction311
- II. Ras Cycle and Ras–Raf Signaling Pathway312
- III. The Structure of Ras Proteins313
- IV. Drug Target Sites of Ras315
- V. Conclusions and Outlook323
- References323
- Chapter 16. Actin-Binding Drugs: MKT-077 and Chaetoglobosin K (CK)329
- I. Introduction329
- II. MKT-077: F-Actin Bundler330
- III. Chaetoglobosin K: F-Actin Capper334
- References338
- Chapter 17. Tyr Kinase Inhibitors as Potential Anticancer Agents: EGF Receptor and ABL Kinases341
- I. Introduction341
- II. Tyr Kinase Inhibitors344
- III. Chronic Myelogenous Leukemia345
- IV. Epidermal Growth Factor Receptor346
- V. Antagonists of the Epidermal Growth Factor Receptor Extracellular Domain347
- VI. Chemical Inhibitors of the Kinase Domain of the Epidermal Growth Factor Receptor348
- VII. Epidermal Growth Factor Receptor Antagonists or Inhibitors Act Synergistically to Kill Tumor Ce350
- VIII. The Effects of Abl Inhibitors on Leukemia352
- References354
- Chapter 18. Antagonists of Rho Family GTPases: Blocking PAKs, ACKs, and Rock361
- I. Rho Family GTPases (Rho, Rac, and CDC42)361
- II. Blocking PAKs362
- III. Blocking CDC42 Pathways (ACKs and N-WASP)370
- IV. Blocking Rho Pathways372
- V. Rac-Specific Inhibitors?374
- References375
- Chapter 19. Integrin Antagonists as Cancer Therapeutics379
- I. Introduction379
- II. Signaling Pathways Activated by Integrins381
- III. Role of Integrins in Neoplastic Transformation384
- IV. Role of Integrins in Tumor-Induced Angiogenesis385
- V. Integrin Antagonists as Antiangiogenesis Agents388
- VI. Conclusions and Future Perspectives391
- References392
- Chapter 20. Functional Rescue of Mutant p53 as a Strategy to Combat Cancer397
- I. Introduction397
- II. Multiple Pathways of p53-Induced Apoptosis398
- III. Regulation of p53 Activity400
- IV. Approaches toward Reactivation of Mutant p53402
- V. Implications for Tumor Therapy and Future Perspectives408
- References411
- Index417
Tumor Suppressing Viruses, Genes, and Drugs profiles the new generation of cancer treatments now in development. The book examines the innovative new approaches of viral, gene, and signal therapies that promise to replace or enhance conventional methods such as surgery, radiation, and chemotherapy. The timely information presented by this book should be of interest to anyone concerned with advancing cancer treatment beyond current medical practices.