18. Molecular basics of carcinogenesis

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Revision as of 14:09, 22 November 2022 by Nikolas (talk | contribs) (Created page with "* DNA damage to normal cell -> mutations in genome -> altered gene product -> Tumor suppressors ↓ or oncogenes ↑ * Protective mechanisms against carcinogenesis ** DNA repair enzymes ** Tumor suppressors * Characteristics of cancer cells ** Inhibition of apoptosis + lack of response to inhibitory factors -> capable of self-maintained replication, long survival ** Mutagenic agents/defective DNA repair -> genetic instability -> more mutations ** Capable of angiogenesis...")
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  • DNA damage to normal cell -> mutations in genome -> altered gene product -> Tumor suppressors ↓ or oncogenes ↑
  • Protective mechanisms against carcinogenesis
    • DNA repair enzymes
    • Tumor suppressors
  • Characteristics of cancer cells
    • Inhibition of apoptosis + lack of response to inhibitory factors -> capable of self-maintained replication, long survival
    • Mutagenic agents/defective DNA repair -> genetic instability -> more mutations
    • Capable of angiogenesis
    • Capable of invasion and metastasis
  • Theories of carcinogenesis
    • Somatic mutation theory (classic theory): cancer results from accumulation of mutations in susceptible cells
      • Process
        • Chemical, radiation, virus, etc. exposure to the cell causes mutations
        • Mutations causes activation of proto-oncogenes and inactivation of tumour suppressor genes
        • Cell transforms from healthy -> pre-cancerous -> cancerous
      • Counterarguments
        • 1: the stroma of the cancer is not mutated but highly influences tumor development, either positively or negatively
        • Healthy cells transplanted to certain cancer stromas will become cancerous
        • Cancer cells transplanted to other cancer stromas will not become more malignant
        • 2: Many cancers acquire mutations first after they become cancerous
    • Cancer stem cell theory
      • Cancer cells arise from stem cells that accumulate damage as they divide
  • Gene dysfunction is not necessarily due to gene mutation – it can also be due to epigenetic malfunction
    • Epigenetic malfunctions are reversible
    • “Epigenetic drugs” reverse these malfunctions
  • Tumour types can be subclassified according to their gene expression
    • These subtypes have different biological properties and diagnosis
    • Examples
      • HER2 positive and negative breast cancer
      • ALK positive and negative lung cancer