History and overview of cancer

• Define cancer

  These are cells that have escaped the normal limitations of external cue driven cell division and have modified their local environment to exceed the natural defined tissue borders. These transformed cells form a multicellular mass and have mechanisms to survive immune surveillance and cell death mechanisms.
• Describe stimulants and limiters of cell growth

  • Growth factors are molecules that bind to specific receptors and promote cell growth, e.g., EGF
  • Hormones can stimulate cell growth, e.g., estrogen
  • Extracellular matrix is a network of proteins that surround cells and can regulate cell growth and division by providing mechanical and chemical signals
  • Chemical microenvironment is the cellular niche where a cell resides and this can limit cell growth
• Describe how cytokines regulate cell growth

  These are small proteins that are released primarily by immune cells and some, such as interleukins and interferons, can promoter cell growth and division and other times suppress. For example, IL1-beta can suppress cancer cell proliferation or promote angiogenesis.
• How do cancer cells manipulate the extracellular matrix?

  • ECM degradation: matrix metalloproteinases
  • ECM remodelling: production and secretion of ECM proteins
  • ECM crosslinking: modifying the ECM proteins by crosslinking
  • ECM receptors: cancer cells can also express receptors on their surface that bind to specific ECM components such as integrins
  • Angiogenesis: cancer cells can promote the formation of new blood vessels
• Describe the formation of transformed cancer cells

  Transformed cells form in a step-wise manner with mutations occurring independently, with the tumour micro environment increasing the frequency of mutations.

  
• Describe how dormant metastases are formed

  Immune cells, such as T-killer cells, eliminate cancer cells. When the immune system can control the growth of the cancer cells, they remain as a dormant metastases. However, as they accumulate mutations and transform, they can proliferate at such a rate that the immune system can no longer control proliferation.

  
• How do cancer cells avoid cell death?

  • Mutations in genes that regulate apoptosis: p53
  • Upregulation of anti-apoptosis proteins: Bcl-2
  • Down regulation of pro-apoptotic proteins: Bax
  • Activation of survival signalling pathways
  • Altering the balancer of death receptors and ligands
• Describe the different cell types that cancer can originate from

  • Epithelial cells: carcinomas
  • Mesenchymal cells: sarcomas
  • Haematopoietic cells: leukaemias
  • Lymphoid cells: lymphoma