Note: Intro -- Foreword -- Preface -- Acknowledgments -- Contents -- Editors and Contributors -- Introduction -- 1 PI3K-Akt-mTOR Signaling in Cancer and Cancer Therapeutics -- Introduction -- The PI3K-Akt-mTOR Signaling Pathway -- PI3K-Akt-mTOR Signaling in Human Physiology: Anabolic Metabolism -- PI3K-Akt-mTOR Signaling in Human Physiology: Regulation of Cell Cycle Progression and Survival -- PI3K-Akt-mTOR in Human Disease: Germline Disorders of Overgrowth and Cancer Susceptibility -- PI3K-Akt-mTOR in Human Disease: Somatic Genetic Mutations in Syndromes of Segmental Overgrowth and Cancer -- Targeting Oncogenic PI3K-Akt-mTOR Signaling for Cancer Therapy -- Clinical Responses to PI3K-Akt-mTOR Inhibitors -- Putative Mechanisms Underlying Suboptimal Drug Responses: Incomplete Pathway Suppression -- Putative Mechanisms Underlying Suboptimal Drug Responses: PI3K Inhibitors Cause Hyperglycemia and Hyperinsulinemia -- Putative Mechanisms Underlying Suboptimal Drug Responses: Drug-Induced Signaling Adaptation and Feedback -- Future Directions: Identifying Effective Drug Combinations -- Conclusion -- Acknowledgments -- References -- Part I PI3K-mTOR Pathway in Cancers -- 2 The mTOR Complexes in Cancer Cell Metabolism -- Introduction -- Glucose Metabolism (Glycolysis) -- Oxidative and Mitochondrial Metabolism -- Glutamine Metabolism -- Amino Acid Metabolism -- Pentose Phosphate Pathway and Nucleotide Synthesis -- Lipid Metabolism -- Acetylation -- Clinical Relevance -- Conclusions and Future Perspectives -- Acknowledgments -- References -- 3 PI3K-AKT-mTOR Pathway Cooperates with the DNA Damage Repair Pathway: Carcinogenesis in Triple-Negative Breast Cancers and Beyond -- Introduction -- Alterations of PI3K-AKT-mTOR Pathway in BC -- Alterations of PI3K-AKT-mTOR Pathway in Subtypes of BC -- Alteration(S) of PI3K-AKT-mTOR Pathway in BC Is Contextual. , PI3K-AKT-mTOR Pathway Alterations in the Context of DNA Damage Response -- DNA Damage in Invasive Carcinoma of Breast: Alterations of DDR Pathway Genes and HRD Genes in Basal-Like BC -- PI3K-AKT-mTOR Pathway and DDR Pathway in Basal-like BC: Protein-Protein Interactions -- 17 PI3K-AKT-mTOR Signaling Pathway Genes: Proteins (Amino Acid -- Aa) and Their Cellular Functions -- 12 DNA Damage Repair Pathway Genes: Proteins and Their Cellular Functions -- PI3K-AKT-mTOR Pathway Inhibition in the Context of DDR: PARP Inhibitors in BC -- PARP Inhibitors as Chemo/Radiopotentiating Agents: TNBC and Beyond -- A Combination of PARP Inhibitors and PI3K-AKT-mTOR Pathway Inhibitors: Drug Sensitivity and Drug Resistance -- Acknowledgments -- References -- 4 The AKT-mTOR Signaling Pathway for Drug Response Prediction and Prognostic Signatures -- The PI3K-AKT-mTOR Signaling Pathway in Cancer: An Overview -- The PI3K-AKT-mTOR Pathway: Kinase Activation and Signaling Cascades -- The PI3K-AKT-mTOR Pathway: Association Between PIK3CA Mutation and Activation of the PI3K-AKT-mTOR Signaling Network -- Activation of the PI3K-AKT-mTOR Signaling Pathway as Prognostic and Predictive Biomarker -- High Throughput Multiplexed Platforms for Functional Analysis of the PI3K-AKT-mTOR Pathway of Clinical Samples -- Antibody-Based Technologies -- Multiplex Immunoassays -- Reverse Phase Protein Microarray -- Phosphoflow -- Tissue Microarrays -- Non-antibody-Based Technologies -- Concluding Remarks -- References -- 5 Resistance to PI3K Pathway Inhibition -- Introduction -- The PI3K-AKT-mTOR Pathway -- Drug-Induced Relief of Feedback Results in Pathway Reactivation -- mTORC1 Inhibition Promotes AKT Activation -- mTORC1 Inhibition Relieves GRB10-Mediated PI3K Suppression -- mTOR Kinase Inhibition Causes Feedback-Dependent Biphasic Regulation of AKT Signaling. , AKT Feedback Regulation of RTK Expression -- Drug-Induced Adaptive/Compensatory Activation of Parallel Signaling Pathways in the Network -- Activation of ERK Signaling -- Coordinated Activation of RAS/RAF Signaling in Resistance -- Feedback Regulation of Nuclear Hormone Signaling -- Wnt-β-Catenin Cooperation with PI3K Signaling -- Myc Amplification -- JAK2/STAT5 Inhibition Circumvents PI3K Resistance -- Additional Implicated Mechanisms of PI3K Resistance, Mechanisms not yet Elucidated -- mTORC1 Inhibition Is Required for Sensitivity to PI3K-Alpha Inhibition -- Inactivating PTEN Mutations Result in PI3K-Beta Hyperactivation -- Mechanisms of Resistance Common to Cellular Signaling Pathways -- Ligand-Mediated Activation of Distinct, Non-inhibited Kinases with Shared Downstream Targets -- Tumor Microenvironment May Confer Targeted Therapy Resistance -- Drug-Resistance-Conferring Oncogene Alterations -- Conclusion and Future Directions -- References -- Part II PI3K-mTOR Pathway in Cancer Medicine -- 6 Combination Therapies Targeting the PI3K/AKT/mTOR Pathways -- Introduction -- Positive Regulators of PI3K/AKT/mTOR Pathways -- PI3K -- Agents Targeting PI3K Isoforms -- AKT -- Agents Targeting AKT -- mTOR Complex -- Agents Targeting mTORC1 -- Dual Kinase Inhibitors -- Negative Regulators of PI3K/AKT/mTOR Pathways -- PTEN -- Tuberous Sclerosis Complex (TSC) and the TSC1-TSC2 Complex -- AMPK -- Toxicity of PI3K/AKT/mTOR Inhibitors -- PI3K/AKT/mTOR Combination Strategies -- PI3K/AKT/mTOR Inhibitor and Chemotherapy -- PI3K/AKT/mTOR Inhibitor and Hormonal Agents -- PI3K/AKT/mTOR Inhibitor and Immunotherapy -- PI3K/AKT/mTOR Inhibitor and Biological Therapy -- Proximal/Distal Inhibition (mTOR Inhibitor and IGF Receptor [IGFR], PI3K, or AKT Inhibitor) -- Parallel Signaling Inhibition -- PI3K/AKT/mTOR Inhibitor and Other Targeted Therapies -- Triple Combinations. , Biomarkers -- Conclusion -- References -- 7 Phospho-Inositol-3-Kinase Activity and Dysregulation in Pediatric Leukemia and Lymphoma -- Introduction -- Phosphatidylinositol-3-Kinase (PI3K)-AKT-mTOR Signaling -- PI3K and Cancer -- The Catalytic Subunit p110δ as a Potential Target in Hematologic Malignancies -- Acute Lymphoblastic Leukemia (ALL) -- Lymphoma -- Acute Myeloid Leukemia (AML) -- Chronic Myeloid Leukemia (CML) -- Juvenile Myelomonocytic Leukemia (JMML) -- Clinical Trials -- Conclusions -- Review Criteria -- Acknowledgements -- References -- 8 HER2 Signaling Network in Advanced Breast Cancer: Opportunities for Combination Therapies -- Background -- The PI3K-AKT-mTOR Pathway in HER2 Positive Breast Cancer -- An Overview of the Pathway -- Involvement of the PI3K Pathway HER2+ Breast Cancer -- Activation of PTEN-PI3K-AKT-mTOR Pathway and Anti-HER2 Therapy Resistance -- PI3K-AKT-mTOR Pathway-Specific Inhibitors Either Approve or Active in Clinical Trial -- Pan HER Inhibitors in HER2+ Breast Cancer -- Conclusion -- Acknowledgments -- References -- 9 The PI3K-mTOR Pathway in Prostate Cancer: Biological Significance and Therapeutic Opportunities -- Introduction -- PI3K-mTOR Signaling and Function -- PI3K-mTOR Signaling in Prostate Cancer -- The PI3K-mTOR Pathway and Epigenetic Programming in Prostate Cancer Pathogenesis -- Crosstalk with AR and Other Signaling in Castration-Resistant Prostate Cancer -- The PI3K-mTOR Pathway in Prostate Cancer Metastasis -- Targeting the PI3K-mTOR Pathway in Prostate Cancer -- PI3K Inhibitors -- AKT Inhibitors -- mTOR Inhibitors -- Dual PI3K-mTOR Inhibitors -- Future Perspectives -- References -- Index.