"...a brave attempt to encompass a broad, exciting and developing field." --MICROBIOLOGY TODAY (2003)

• ContributorsPreface1 Oncolytic Viruses: Virotherapy for CancerI. IntroductionII. Attributes of Replication-Selective Viruses for Cancer TreatmentIII. Approaches to Optimizing Tumor-Selective Viral ReplicationIV. AdenovirusesV. PoliovirusVI. Vesicular Stomatitis VirusVII. ReovirusVIII. BacteriaIX. Vaccinia VirusX. HerpesvirusXI. Clinical Trial Results with Replication-Competent Adenoviruses in Cancer PatientsXII. Results from Clinical Trials with dl1520 (Onyx-015, or CI-1042)XIII. Future Directions: Approaches to Improving the Efficacy of Replication-Selective Viral AgentsXIV. SummaryReferences2 Reovirus Therapy of Ras-Associated CancersI. IntroductionII. Reovirus OncolysisIII. Concluding RemarksReferences3 Oncolytic Herpes Simplex Virus (G207) Therapy: From Basic to ClinicalI. IntroductionII. Preclinical Studies of G207III. G207 Clinical TrialIV. ConclusionsReferences4 p53 and Its TargetsI. IntroductionII. Activation of p53III. Downstream Mediators of p53References5 Prospects for Tumor Suppressor Gene Therapy: RB as an ExampleI. IntroductionII. Functions of RBIII. Successes with RB Gene Therapy IV. PerspectivesReferences6 CDK Inhibitors: Genes and DrugsI. IntroductionII. G1 Regulation III. p16INK4a and the Rb PathwayIV. p19ARF and p53 PathwayV. p27 and Human CancerVI. Conclusions and Future PerspectivesReferences7 CDK Inhibitors: Small Molecular Weight CompoundsI. IntroductionII. Cyclin-Dependent Kinases, the Cell Cycle, and CancerIII. Cyclin-Dependent Kinase Inhibitors, a Large Variety of StructuresIV. Cyclin-Dependent Kinase Inhibitors, All Competing with ATPV. Cyclin-Dependent Kinase Inhibitors, the Selectivity ProblemVI. Cyclin-Dependent Kinase Inhibitors, Cellular EffectsVII. Cyclin-Dependent Kinase Inhibitors, Antitumor ActivityVIII. ConclusionReferences8 NF1 and Other RAS-Binding PeptidesI. RAS Molecules: Normal versus Oncogenic Mutants II. Super GAP?III. RAS-Binding Fragment of NF1IV. c-RAF-1V. PI-3 KinaseVI. Ral GDS References9 Cytoskeletal Tumor Suppressor GenesI. Introduction (Historical Background)II. Type I Cytoskeletal Tumor SuppressorsIII. Type II Cytoskeletal Tumor SuppressorsReferences10 TGF-? Signaling and CarcinogenesisI. IntroductionII. Dual Role of TGF-? in CarcinogenesisIII. TGF-? Superfamily SignalingIV. Perturbation of TGF-? Signaling in Cancer CellsV. PerspectivesReferences11 DAN GeneI. IntroductionII. Cloning of DAN cDNAIII. Transfection of DANIV. Role of DAN in NeuroblastomasV. Structural Features of the DAN ProteinVI. Genomic Structure of DANVII. DAN FamilyReferences12 Design of Hammerhead Ribozymes and Allosterically Controllable Maxizymes for Cancer Gene TherapyI. IntroductionII. Ribozyme Expression System in CellsIII. Design of the tRNAVal-Driven Ribozyme That Is Transcribed by pol IIIIV. Design of Allosterically Controlled MaxizymesV. ConclusionReferences13 Inhibitors of AngiogenesisI. Introduction—AngiogenesisII. Angiogenesis InhibitorsIII. Future DirectionsReferences14 Geranylgeranylated RhoB Mediates the Apoptotic and Antineoplastic Effects of Farnesyltransferase Inhibitors: New Insights into Cancer Cell SuicideI. Introduction II. Do Farnesyltransferase Inhibitors Target a Unique Aspect of Neoplastic Pathophysiology?III. Ras Is Not a Crucial Target of Farnesyltransferase InhibitorsIV. RhoB Is a Crucial Target of Farnesyltransferase InhibitorsV. Farnesyltransferase Inhibitors Act through a Gain of Function Mechanism Involving RhoB-GGVI. RhoB-GG Is Required to Mediate Apoptosis by Farnesyltransferase InhibitorsVII. RhoB-GG and the Antiangiogenic Properties of Farnesyltransferase InhibitorsVIII. Clinical ImplicationsIX. SummaryReferences15 RAS Binding CompoundsI. IntroductionII. Ras Cycle and Ras–Raf Signaling PathwayIII. The Structure of Ras ProteinsIV. Drug Target Sites of RasV. Conclusions and OutlookReferences16 Actin-Binding Drugs: MKT-077 and Chaetoglobosin K (CK)I. IntroductionII. MKT-077: F-Actin BundlerIII. Chaetoglobosin K: F-Actin CapperReferences17 Tyr Kinase Inhibitors as Potential Anticancer Agents: EGF Receptor and ABL KinasesI. IntroductionII. Tyr Kinase InhibitorsIII. Chronic Myelogenous LeukemiaIV. Epidermal Growth Factor ReceptorV. Antagonists of the Epidermal Growth Factor Receptor Extracellular DomainVI. Chemical Inhibitors of the Kinase Domain of the Epidermal Growth Factor ReceptorVII. Epidermal Growth Factor Receptor Antagonists or Inhibitors Act Synergistically to Kill Tumor CellsVIII. The Effects of Abl Inhibitors on LeukemiaReferences18 Antagonists of Rho Family GTPases: Blocking PAKs, ACKs, and RockI. Rho Family GTPases (Rho, Rac, and CDC42)II. Blocking PAKsIII. Blocking CDC42 Pathways (ACKs and N-WASP)IV. Blocking Rho PathwaysV. Rac-Specific Inhibitors?References19 Integrin Antagonists as Cancer TherapeuticsI. IntroductionII. Signaling Pathways Activated by IntegrinsInII. Role of Integrins in Neoplastic TransformatioIV. Role of Integrins in Tumor-Induced AngiogenesisV. Integrin Antagonists as Antiangiogenesis AgentsVI. Conclusions and Future PerspectivesReferences20 Functional Rescue of Mutant p53 as a Strategy to Combat CancerI. Introduction II. Multiple Pathways of p53-Induced ApoptosisIII. Regulation of p53 ActivityIV. Approaches toward Reactivation of Mutant p53V. Implications for Tumor Therapy and Future PerspectivesReferencesIndex