Cancer Biology

  1. The Hallmarks of Cancer
    1. Sustaining Proliferative Signaling
      1. Growth Factor Independence
        1. Autocrine Signaling Loops
          1. Paracrine Stimulation
          2. Growth Factor Receptor Alterations
            1. Overexpression
              1. Constitutive Activation
                1. Ligand-Independent Signaling
                2. Downstream Pathway Activation
                  1. MAPK Pathway
                    1. RAS Activation
                      1. RAF/MEK/ERK Cascade
                      2. PI3K/AKT Pathway
                        1. PIP3 Generation
                          1. AKT Activation
                            1. mTOR Signaling
                            2. JAK/STAT Pathway
                              1. Cytokine Signaling
                                1. Transcriptional Activation
                            3. Evading Growth Suppressors
                              1. RB Pathway Disruption
                                1. Cyclin D Overexpression
                                  1. CDK4/6 Activation
                                    1. p16 Inactivation
                                    2. p53 Pathway Inactivation
                                      1. p53 Mutations
                                        1. MDM2 Amplification
                                          1. p14ARF Loss
                                          2. Contact Inhibition Loss
                                            1. Cell-Cell Adhesion Defects
                                              1. Density-Dependent Growth Control
                                              2. TGF-β Resistance
                                                1. Receptor Mutations
                                                  1. SMAD Inactivation
                                                2. Resisting Cell Death
                                                  1. Apoptosis Evasion
                                                    1. p53 Inactivation
                                                      1. BCL-2 Overexpression
                                                        1. Death Receptor Defects
                                                          1. Caspase Inhibition
                                                          2. Autophagy Modulation
                                                            1. Autophagy Inhibition
                                                              1. Autophagy Dependence
                                                              2. Necroptosis Resistance
                                                                1. RIPK3 Loss
                                                                  1. Caspase-8 Activation
                                                                2. Enabling Replicative Immortality
                                                                  1. Telomere Biology
                                                                    1. Telomere Structure
                                                                      1. Telomere Shortening
                                                                        1. Senescence Induction
                                                                        2. Telomerase Activation
                                                                          1. TERT Expression
                                                                            1. TR Component
                                                                              1. Telomerase Assembly
                                                                              2. Alternative Lengthening of Telomeres
                                                                                1. Homologous Recombination
                                                                                  1. ALT-Associated PML Bodies
                                                                                    1. ATRX/DAXX Mutations
                                                                                  2. Inducing Angiogenesis
                                                                                    1. Angiogenic Switch
                                                                                      1. Hypoxia Response
                                                                                        1. Metabolic Stress
                                                                                          1. Oncogene Activation
                                                                                          2. Pro-angiogenic Factors
                                                                                            1. Vascular Endothelial Growth Factor
                                                                                              1. VEGF-A
                                                                                                1. VEGF Receptors
                                                                                                  1. Signaling Pathways
                                                                                                  2. Fibroblast Growth Factor
                                                                                                    1. FGF2
                                                                                                      1. FGF Receptors
                                                                                                      2. Angiopoietins
                                                                                                        1. Tie Receptors
                                                                                                          1. Vessel Maturation
                                                                                                        2. Anti-angiogenic Factors
                                                                                                          1. Thrombospondin-1
                                                                                                            1. Angiostatin
                                                                                                              1. Endostatin
                                                                                                              2. Tumor Vasculature Characteristics
                                                                                                                1. Abnormal Architecture
                                                                                                                  1. Increased Permeability
                                                                                                                    1. Poor Perfusion
                                                                                                                  2. Activating Invasion and Metastasis
                                                                                                                    1. Epithelial-Mesenchymal Transition
                                                                                                                      1. EMT Transcription Factors
                                                                                                                        1. SNAIL
                                                                                                                          1. SLUG
                                                                                                                            1. TWIST
                                                                                                                              1. ZEB1/ZEB2
                                                                                                                              2. Loss of Epithelial Markers
                                                                                                                                1. E-cadherin Downregulation
                                                                                                                                  1. Tight Junction Disruption
                                                                                                                                  2. Gain of Mesenchymal Markers
                                                                                                                                    1. Vimentin Expression
                                                                                                                                      1. N-cadherin Upregulation
                                                                                                                                    2. Cell Adhesion Changes
                                                                                                                                      1. Cadherin-Catenin Complex
                                                                                                                                        1. Integrin Switching
                                                                                                                                          1. Selectin Interactions
                                                                                                                                          2. Extracellular Matrix Remodeling
                                                                                                                                            1. Matrix Metalloproteinases
                                                                                                                                              1. MMP2
                                                                                                                                                1. MMP9
                                                                                                                                                  1. MMP14
                                                                                                                                                  2. Serine Proteases
                                                                                                                                                    1. uPA System
                                                                                                                                                      1. Plasmin Generation
                                                                                                                                                      2. ECM Component Changes
                                                                                                                                                        1. Collagen Remodeling
                                                                                                                                                          1. Fibronectin Deposition
                                                                                                                                                        2. Motility and Migration
                                                                                                                                                          1. Actin Cytoskeleton Reorganization
                                                                                                                                                            1. Focal Adhesion Dynamics
                                                                                                                                                              1. Rho GTPase Signaling
                                                                                                                                                            2. Emerging Hallmarks
                                                                                                                                                              1. Deregulating Cellular Energetics
                                                                                                                                                                1. Warburg Effect
                                                                                                                                                                  1. Aerobic Glycolysis
                                                                                                                                                                    1. Lactate Production
                                                                                                                                                                      1. pH Regulation
                                                                                                                                                                      2. Glutamine Metabolism
                                                                                                                                                                        1. Glutaminolysis
                                                                                                                                                                          1. Nitrogen Source
                                                                                                                                                                          2. Fatty Acid Metabolism
                                                                                                                                                                            1. Lipogenesis
                                                                                                                                                                              1. β-oxidation
                                                                                                                                                                              2. Metabolic Reprogramming
                                                                                                                                                                                1. Enzyme Expression Changes
                                                                                                                                                                                  1. Metabolic Flexibility
                                                                                                                                                                                2. Avoiding Immune Destruction
                                                                                                                                                                                  1. Immune Checkpoint Exploitation
                                                                                                                                                                                    1. PD-1/PD-L1 Axis
                                                                                                                                                                                      1. CTLA-4 Signaling
                                                                                                                                                                                      2. Antigen Presentation Defects
                                                                                                                                                                                        1. MHC Class I Loss
                                                                                                                                                                                          1. Antigen Processing Defects
                                                                                                                                                                                          2. Immunosuppressive Factors
                                                                                                                                                                                            1. TGF-β Secretion
                                                                                                                                                                                              1. IL-10 Production
                                                                                                                                                                                                1. IDO Expression
                                                                                                                                                                                                2. Regulatory Cell Recruitment
                                                                                                                                                                                                  1. Tregs
                                                                                                                                                                                                    1. MDSCs
                                                                                                                                                                                                      1. M2 Macrophages
                                                                                                                                                                                                    2. Tumor-Promoting Inflammation
                                                                                                                                                                                                      1. Inflammatory Cytokines
                                                                                                                                                                                                        1. TNF-α
                                                                                                                                                                                                          1. IL-6
                                                                                                                                                                                                            1. IL-1β
                                                                                                                                                                                                            2. NF-κB Activation
                                                                                                                                                                                                              1. Inflammatory Gene Expression
                                                                                                                                                                                                                1. Survival Signaling
                                                                                                                                                                                                                2. Complement Activation
                                                                                                                                                                                                                  1. C5a Signaling
                                                                                                                                                                                                                    1. Immune Complex Formation
                                                                                                                                                                                                                  2. Genome Instability and Mutation
                                                                                                                                                                                                                    1. DNA Repair Defects
                                                                                                                                                                                                                      1. Mismatch Repair Loss
                                                                                                                                                                                                                        1. Homologous Recombination Deficiency
                                                                                                                                                                                                                        2. Replication Stress
                                                                                                                                                                                                                          1. Oncogene-Induced Stress
                                                                                                                                                                                                                            1. Fork Stalling and Collapse
                                                                                                                                                                                                                            2. Mutator Phenotypes
                                                                                                                                                                                                                              1. High Mutation Rates
                                                                                                                                                                                                                                1. Clonal Evolution

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                                                                                                                                                                                                                          3. The Genetic and Epigenetic Landscape of Cancer

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                                                                                                                                                                                                                          5. Tumor Microenvironment