Oncogenes and tumour suppressors 2

• Describe HER2 expression in breast cancer

  HER2 is a proto-oncogen that is overexpressed in breast cancer. This is a RTK that induces Proliferative and anti-apoptotic signals.
• Describe the structure of RTKs

  They consists of:

  • extracellular ligand binding region
  • transmembrane region
  • intracellular tyrosine kinase domain

  Upon activation, they dimerise and autophosphorylate themselves, leading to activation of the Ras MAPK pathway.
• Describe drugs that can target HER2 activity

  Antibodies can be used to block the action of HER2, which prevents activation of the Ras MAPK pathway. Other drugs include:

  • Pertuzumab: which inhibits the dimerisation of HER2
  • Trastuzumab: antibody that inhibits via direct binding
• Describe the step-wise manner of cancer transformation

  1. LOF Mutation in negative cell cycle regulator
  2. GOF Mutation in positive cell cycle regulator
  3. Mutation leading to inhibition of cell death
  4. TME increases mutational rate