Progression

• Once a cell has been initiated + specifically expanded by promoters

  • the altered cell can either
  • Regress following promoter removal/ Experience another genetic & epigenetic event to facilitate tumor progression
• Progression = a state of genomic instability presented by multiple mutations

  • Genomic instability = More aggressive phenotype
  • Increase tumor size + Invasiveness + Metastasis + Increase growth rate
• The clonal nature of the neoplastic lesion = lost

  • the neoplasm: composed of diff cell types and extracellular matrix
• Non-malignant epithelial tissue

  • Supported by a stroma composed of = Extracellular matrix, Fibroblasts, MSCs
• Tumor tissue

  • Stroma become fibrotic + activated
• Tumor tissue

  • ECM:
  • Denser, more rigid
  • Composed of alternative forms of connective fibres --> cancer cell invade thru
• Tumor tissue

  • Fibroblasts & MCS:
  • Change shape and expression profiles
  • More proliferative
  • Secrete more growth factors
• Stroma fibroblasts in tumor env. = Cancer-associated fibroblasts

  • Promote cancer progression and metastasis
• Grading stage: Level of metastasis
• • Most cancer cells = Monoclonal (derived from a single cell)
  • Arise from accumulation of mutations in a single cell (not single mutation)
  • Usually 3 - 7 mutations (hits) required for cancer development
  • Each additional mutation provides further growth advantage for the developing tumor
• Mutation in both proto-oncogenes + tumor suppressor gene required for cancer to occur
• Mutation to one oncogene: suppressed by normal mitotic control + tumor suppressor gene
• Mutation to one tumor suppressor gene: not cancer b/c many backup agents duplicate its function
• Only when enough proto-oncogenes mutated into oncogenes + enough tumor suppressor genes deactivated or damaged --> signals for cell growth overwhelm the signals to regulate it --> uncontrolled cell growth