Lesson 15 Oncogenic Inflammation & Anti-Inflammatory drugs

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• Innate immune cells


  Mediate inflammatory responses to injury, infection

  
• Inflammatory responses

  • Inflammatory cytokines also trigger proliferation to replace damaged/dead cells
  • Widening of blood vessels
  • Heightened pain sensitivity

  
• Pathogen-associated molecular patterns


  Trigger inflammatory responses

  
• Damage-associated molecular patterns


  Trigger inflammatory responses

  
• Continued inflammation can be oncogenic
• Inflammation

  • Allows repair of injured/infected tissue: removal of debris and restoration of normal tissue structure
  • When inflammation continues indefinitely, proliferative and angiogenic processes that enable wound repair can encourage cancer development
• Exposure to environmental irritants and infections


  Provokes inflammation, which (if not resolved) can encourage cancer development
• Cancers, and cellular damage provoked by treatment

  Can stimulate immune cells to secrete inflammatory cytokines
• Inflammation


  Cancer (treatment) → inflammation → cancer progression etc

  
• Infection by the bacteria H. pylori triggers chronic inflammation in the stomach which can cause ulcers and (ultimately) cancers
• Stomach cancers are a rare consequence of H. pylori infection
• Half of the world's population have H. pylori infections. Of those: 10% develop peptic ulcers, A small proportion (~3%) develop cancer

  
• Resolve inflammation to prevent cancer development or progression
• Curing H pylori infection eliminated many low grade MALT lymphomas and halved the risk of gastric carcinomas
• Japan has recommended treating H. pylori infections since 2000, which has helped to reduce the mortality due to gastric cancers
• Observational studies suggested aspirin may reduce the risk of gastro-intestinal tract cancers by about 25%, but confounders may have affected those results
• Randomised controlled trials are the best way of determining the true effect of an exposure (like aspirin) on cancer incidence
• A few RCTs concluded that aspirin usage could reduce cancer risk in particular contexts, e.g. patients with a cancer pre-disposition syndrome
• A 2020 meta-analysis of 29 RCTs concluded that long term aspirin consumption did not alter cancer incidence or mortality, but did promote bleeding
• Lynch syndrome individuals are recommended to take aspirin to reduce their risk of developing colorectal cancer
• For individuals with standard cancer risk, the adverse effects of aspirin probably outweigh any potential cancer suppression benefits
• Chemotherapy can be inflammatory and cause nausea and vomiting, which can be reduced by anti-inflammatory drugs
• Anti-inflammatory drugs can improve quality of life of patients and enable higher doses of chemotherapy to be given, boosting survival rates