Metabolic alterations in cancer

  • Created by: -FlIp
  • Created on: 01-08-18 12:48
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  • Metabolic alterations in cancer
    • Hallmarks of cancer
      • Hanahan and Weinberg (2000)
        • evading apoptosis
        • self-sufficiency in growth signals
        • insensitivity to anti-growth signals
        • tissue invasion & metastasis
        • limitless replicative potential
        • sustained angiogenesis (development of new blood vessels)
        • 2011 updates
          • emerging hallmarks
            • deregulating cellular energetics
            • avoiding immune destruction
            • self-sufficiency in growth signals
            • insensitivity to anti-growth signals
          • enabling characteristics
            • genome instability & mutation
            • tumour promoting inlammation
            • sustained angiogenesis
    • Oncogenes, tumour suppressors & tumour environment leads to alterations in cellular metabolism
    • Warnburg effect
      • shift from oxidative phosphorylation to aerobic glycolysis
      • a reliance on glycolysis for ATP generation even under normal oxygen levels
      • an aerobic glycolytic switch first noted by Otto Warburg in 1920s
      • increased lactate output
        • essentially establishes a Cori cycle
      • His reasoning that this effect was due to mitochondrial malfunction was incorrect
        • capacity and function of mitochondrial pathways remains the same
      • relatively inefficient
        • 2ATP produced per cycle
        • large difference in ATP produced per molecule of glucose
        • glycolysis is faster than full oxidative phos.
      • pyruvate is largely converted into lactate by the cori cycle with the liver in tumours
        • lactic acid produced goes to the liver & is converted to glucose

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