1;Therapeutic Ribonucleic Acids in Brain Tumors;2 1.1;Preface;5 1.2;Contents;9 1.3;Contributors;11 1.4;Molecular Biology of Malignant Gliomas;17 1.4.1;1 Introduction;18 1.4.2;2 Altered Pathways Involved in Human Gliomas;19 1.4.2.1;2.1 pRb/E2F Axis in Human Gliomas;19 1.4.2.2;2.2 P53/MDM2/p14-ARF;20 1.4.2.3;2.3 PI3K/PTEN/Akt/PKB;25 1.4.2.4;2.4 EGFR;25 1.4.2.5;2.5 PDGF and PDGFR;27 1.4.2.6;2.6 VEGFR;27 1.4.2.7;2.7 K-Ras/Raf/MAPK;27 1.4.3;3 Lessons from Microarray Studies;28 1.4.4;4 Glioma Stem-Like Cells;33 1.4.5;5 Challenges for Therapies;35 1.4.6;References;35 1.5;Molecular Neurooncology and Neoangiogenesis of Malignant Gliomas;39 1.5.1;1 Molecular Pathways in Malignant Gliomas;41 1.5.1.1;1.1 Genetic Pathways of Primary (De Novo) and Secondary Glioblastomas;42 1.5.1.2;1.2 Major Signaling Pathways Regulating Tumor Growth;46 1.5.1.2.1;1.2.1 EGF/EGFR Signaling Pathway;46 1.5.1.2.2;1.2.2 PDGF/PDGFR Signaling Pathway;48 1.5.1.2.3;1.2.3 TGF/TGF-R Signaling Pathway;48 1.5.1.2.4;1.2.4 FGF/FGFR Signaling Pathway;50 1.5.1.2.5;1.2.5 IGF/IGFR Signaling Pathway;50 1.5.1.2.6;1.2.6 Gas6/Axl Signaling Pathway;50 1.5.1.3;1.3 Major Signaling Pathways Regulating Tumor-Angiogenesis;51 1.5.1.3.1;1.3.1 VEGF/VEGFR Signaling Pathway;51 1.5.1.3.2;1.3.2 Angiopoietins;53 1.5.1.3.3;1.3.3 Integrins;53 1.5.1.4;1.4 Major Intracellular Signal Transduction Pathways;54 1.5.1.4.1;1.4.1 Ras Signal Transduction;54 1.5.1.4.2;1.4.2 PI3K/Akt/PTEN/mTOR Signaling Pathway;54 1.5.2;2 Neoangiogenesis in Malignant Gliomas;55 1.5.2.1;2.1 Cellular Mechanisms;56 1.5.2.2;2.2 Molecular Mechanisms;56 1.5.2.3;2.3 Structural Abnormalities of Brain Tumor Blood Vessels and Blood Brain Barrier;58 1.5.2.4;2.4 Tumor Edema in Malignant Gliomas;60 1.5.2.4.1;Attendum;60 1.5.2.4.1.1;Growth Factor Receptors;60 1.5.2.4.1.2;Ras-GDP Pathway;60 1.5.2.4.1.3;PI3K Pathway;61 1.5.3;References;62 1.6;Molecular Therapies for Malignant Gliomas;72 1.6.1;1 Principles of Molecular Targeted Therapies;74 1.6.1.1;1.1 Monoclonal Antibodies;74 1.6.1.2;1.2 Small Molecule Inhibitors;75 1.6.1.3;1.3 Antisense Oligodeoxy-Nucleotides;75 1.6.1.4;1.4 Obstacles to Successful Targeted Therapyof Malignant Gliomas;76 1.6.2;2 Preclinical and Clinical Studies of Molecular Therapies in Malignant Gliomas;77 1.6.2.1;2.1 Targeting Receptor Tyrosine Kinase Signaling Pathways;77 1.6.2.1.1;2.1.1 Targeting the PDGF/PDGFR Signaling Pathway;77 1.6.2.1.2;2.1.2 Targeting the EGF/EGFR Signaling Pathway;83 1.6.2.1.3;2.1.3 Targeting the FGF/FGFR Signaling Pathway;84 1.6.2.1.4;2.1.4 Targeting the IGF/IGFR Signaling Pathway;84 1.6.2.1.5;2.1.5 Targeting Intracellular Signaling Pathways;84 1.6.2.2;2.2 Multitargeting Small Molecule Inhibitors;85 1.6.2.3;2.3 Antiangiogenic Treatment in Malignant Gliomas;88 1.6.2.3.1;2.3.1 Antiangiogenic Treatment Regimes Used in Malignant Gliomas;89 1.6.2.3.2;2.3.2 Effects of Antiangiogenic Treatment on Brain Tumor Edema;90 1.6.2.3.3;2.3.3 Evaluation of Brain Tumor Response to AntiangiogenicTherapy Approaches;90 1.6.2.3.4;2.3.4 Potential CNS Toxicity of Antiangiogenic Agents;92 1.6.2.4;2.4 Targeting TGF-Beta: Antisense Oligodeoxynucleotide Therapy Approaches of Malignant Gliomas;92 1.6.3;3 Conclusions and Future Directions;93 1.6.4;References;94 1.7;Novel Strategies for the Treatment of Brain Cancer;100 1.7.1;1 Introduction;101 1.7.2;2 Current Management of GBM;101 1.7.3;3 Molecular Pathomechanism of GBM as the Basis for Innovative Treatments;101 1.7.3.1;3.1 Signaling Pathways in GBM as Therapeutic Targets;102 1.7.3.2;3.2 Cancer Stem Cells and GBM;102 1.7.4;4 Innovative Strategies for the Treatment of GBM;103 1.7.4.1;4.1 Antiangiogenesis Approaches for Treatment of GBM;103 1.7.4.2;4.2 Innovations in Drug Delivery to GBM;107 1.7.4.2.1;4.2.1 Anticancer Agents with Increased Penetrationof Blood-Brain Tumor Barrier;107 1.7.4.2.2;4.2.2 Local Delivery of Chemotherapeutic Agents into the Tumor;108 1.7.4.2.3;4.2.3 Convection-Enhanced Delivery;109 1.7.4.2.4;4.2.4 Liposomes for Drug Delivery to GBM;109 1.7.4.2.5;4.2.5