Tumor Suppressing Viruses, Genes, and Drugs

  • ID: 1765287
  • Book
  • 425 Pages
  • Elsevier Science and Technology
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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.

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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
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Maruta, Hiroshi
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