| Contributors | p. xi |
| Preface | p. xv |
| Oncolytic Viruses: Virotherapy for Cancer | p. 1 |
| Introduction | p. 2 |
| Attributes of Replication-Selective Viruses for Cancer Treatment | p. 4 |
| Approaches to Optimizing Tumor-Selective Viral Replication | p. 4 |
| Adenoviruses | p. 5 |
| Poliovirus | p. 7 |
| Vesicular Stomatitis Virus | p. 8 |
| Reovirus | p. 8 |
| Bacteria | p. 9 |
| Vaccinia Virus | p. 10 |
| Herpesvirus | p. 12 |
| Clinical Trial Results with Replication-Competent Adenoviruses in Cancer Patients | p. 16 |
| Results from Clinical Trials with dl1520 (Onyx-015, or CI-1042) | p. 18 |
| Future Directions: Approaches to Improving the Efficacy of Replication-Selective Viral Agents | p. 23 |
| Summary | p. 24 |
| References | p. 24 |
| Reovirus Therapy of Ras-Associated Cancers | p. 31 |
| Introduction | p. 31 |
| Reovirus Oncolysis | p. 34 |
| Concluding Remarks | p. 40 |
| References | p. 41 |
| Oncolytic Herpes Simplex Virus (G207) Therapy: From Basic to Clinical | p. 45 |
| Introduction | p. 45 |
| Preclinical Studies of G207 | p. 48 |
| G207 Clinical Trial | p. 65 |
| Conclusions | p. 67 |
| References | p. 68 |
| p53 and Its Targets | p. 77 |
| Introduction | p. 77 |
| Activation of p53 | p. 78 |
| Downstream Mediators of p53 | p. 81 |
| References | p. 90 |
| Prospects for Tumor Suppressor Gene Therapy: RB as an Example | p. 97 |
| Introduction | p. 97 |
| Functions of RB | p. 100 |
| Successes with RB Gene Therapy | p. 110 |
| Perspectives | p. 113 |
| References | p. 115 |
| CDK Inhibitors: Genes and Drugs | p. 123 |
| Introduction | p. 123 |
| G1 Regulation | p. 124 |
| p16[superscript INK4a] and the Rb Pathway | p. 131 |
| p19[superscript ARF] and p53 Pathway | p. 133 |
| p27 and Human Cancer | p. 135 |
| Conclusions and Future Perspectives | p. 136 |
| References | p. 137 |
| CDK Inhibitors: Small Molecular Weight Compounds | p. 145 |
| Introduction | p. 145 |
| Cylin-Dependent Kinases, the Cell Cycle, and Cancer | p. 146 |
| Cyclin-Dependent Kinase Inhibitors, a Large Variety of Structures | p. 149 |
| Cyclin-Dependent Kinase Inhibitors, All Competing with ATP | p. 151 |
| Cyclin-Dependent Kinase Inhibitors, the Selectivity Problem | p. 152 |
| Cyclin-Dependent Kinase Inhibitors, Cellular Effects | p. 154 |
| Cyclin-Dependent Kinase Inhibitors, Antitumor Activity | p. 155 |
| Conclusion | p. 161 |
| References | p. 162 |
| NF1 and Other RAS-Binding Peptides | p. 169 |
| RAS Molecules: Normal versus Oncogenic Mutants | p. 169 |
| Super GAP? | p. 170 |
| RAS-Binding Fragment of NF1 | p. 171 |
| c-RAF-1 | p. 172 |
| PI-3 Kinase | p. 173 |
| Ral GDS | p. 173 |
| References | p. 174 |
| Cytoskeletal Tumor Suppressor Genes | p. 177 |
| Introduction (Historical Background) | p. 177 |
| Type I Cytoskeletal Tumor Suppressors | p. 179 |
| Type II Cytoskeletal Tumor Suppressors | p. 186 |
| References | p. 192 |
| TGF-[beta] Signaling and Carcinogenesis | p. 199 |
| Introduction | p. 199 |
| Dual Role of TGF-[beta] in Carcinogenesis | p. 200 |
| TGF-[beta] Superfamily Signaling | p. 200 |
| Perturbation of TGF-[beta] Signaling in Cancer Cells | p. 207 |
| Perspectives | p. 212 |
| References | p. 213 |
| DAN Gene | p. 221 |
| Introduction | p. 221 |
| Cloning of DAN cDNA | p. 222 |
| Transfection of DAN | p. 223 |
| Role of DAN in Neuroblastomas | p. 223 |
| Structural Features of the DAN Protein | p. 225 |
| Genomic Structure of DAN | p. 228 |
| DAN Family | p. 228 |
| References | p. 231 |
| Design of Hammerhead Ribozymes and Allosterically Controllable Maxizymes for Cancer Gene Therapy | p. 233 |
| Introduction | p. 233 |
| Ribozyme Expression System in Cells | p. 236 |
| Design of the tRNA[superscript Val]-Driven Ribozyme That Is Transcribed by pol III | p. 240 |
| Design of Allosterically Controlled Maxizymes | p. 246 |
| Conclusion | p. 255 |
| References | p. 256 |
| Inhibitors of Angiogenesis | p. 261 |
| Introduction--Angiogenesis | p. 261 |
| Angiogenesis Inhibitors | p. 265 |
| Future Directions | p. 274 |
| References | p. 276 |
| Geranylgeranylated RhoB Mediates the Apoptotic and Antineoplastic Effects of Farnesyltransferase Inhibitors: New Insights into Cancer Cell Suicide | p. 293 |
| Introduction | p. 293 |
| Do Farnesyltransferase Inhibitors Target a Unique Aspect of Neoplastic Pathophysiology? | p. 294 |
| Ras Is Not a Crucial Target of Farnesyltransferase Inhibitors | p. 294 |
| RhoB Is a Crucial Target of Farnesyltransferase Inhibitors | p. 295 |
| Farnesyltransferase Inhibitors Act through a Gain of Function Mechanism Involving RhoB-GG | p. 297 |
| RhoB-GG Is Required to Mediate Apoptosis by Farnesyltransferase Inhibitors | p. 298 |
| RhoB-GG and the Antiangiogenic Properties of Farnesyltransferase Inhibitors | p. 302 |
| Clinical Implications | p. 302 |
| Summary | p. 304 |
| References | p. 305 |
| RAS Binding Compounds | p. 311 |
| Introduction | p. 311 |
| Ras Cycle and Ras-Raf Signaling Pathway | p. 312 |
| The Structure of Ras Proteins | p. 313 |
| Drug Target Sites of Ras | p. 315 |
| Conclusions and Outlook | p. 323 |
| References | p. 323 |
| Actin-Binding Drugs: MKT-077 and Chaetoglobosin K (CK) | p. 329 |
| Introduction | p. 329 |
| MKT-077: F-Actin Bundler | p. 330 |
| Chaetoglobosin K: F-Actin Capper | p. 334 |
| References | p. 338 |
| Tyr Kinase Inhibitors as Potential Anticancer Agents: EGF Receptor and ABL Kinases | p. 341 |
| Introduction | p. 341 |
| Tyr Kinase Inhibitors | p. 344 |
| Chronic Myelogenous Leukemia | p. 345 |
| Epidermal Growth Factor Receptor | p. 346 |
| Antagonists of the Epidermal Growth Factor Receptor Extracellular Domain | p. 347 |
| Chemical Inhibitors of the Kinase Domain of the Epidermal Growth Factor Receptor | p. 348 |
| Epidermal Growth Factor Receptor Antagonists or Inhibitors Act Synergistically to Kill Tumor Cells | p. 350 |
| The Effects of Abl Inhibitors on Leukemia | p. 352 |
| References | p. 354 |
| Antagonists of Rho Family GTPases: Blocking PAKs, ACKs, and Rock | p. 361 |
| Rho Family GTPases (Rho, Rac, and CDC42) | p. 361 |
| Blocking PAKs | p. 362 |
| Blocking CDC42 Pathways (ACKs and N-WASP) | p. 370 |
| Blocking Rho Pathways | p. 372 |
| Rac-Specific Inhibitors? | p. 374 |
| References | p. 375 |
| Integrin Antagonists as Cancer Therapeutics | p. 379 |
| Introduction | p. 379 |
| Signaling Pathways Activated by Integrins | p. 381 |
| Role of Integrins in Neoplastic Transformation | p. 384 |
| Role of Integrins in Tumor-Induced Angiogenesis | p. 385 |
| Integrin Antagonists as Antiangiogenesis Agents | p. 388 |
| Conclusions and Future Perspectives | p. 391 |
| References | p. 392 |
| Functional Rescue of Mutant p53 as a Strategy to Combat Cancer | p. 397 |
| Introduction | p. 397 |
| Multiple Pathways of p53-Induced Apoptosis | p. 398 |
| Regulation of p53 Activity | p. 400 |
| Approaches toward Reactivation of Mutant p53 | p. 402 |
| Implications for Tumor Therapy and Future Perspectives | p. 408 |
| References | p. 411 |
| Index | p. 417 |
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