Evolution of HER-2 Targeted Therapies

  • The development of the monoclonal antibody trastuzumab (Herceptin):
    • Has revolutionized the treatment of patients with HER-2-positive breast cancer
  • The exact mechanism of action of trastuzumab remains unclear:
    • It is postulated that its action includes:
      • Antibody-dependent cellular toxicity
      • Inhibition of cell cycle progression
        • Anti-angiogenic effects
  • The use of trastuzumab was first approved by the Food and Drug Administration (FDA) in 1998:
    • For the treatment of HER-2-positive metastatic disease:
      • Since that time, drug testing progressed to the adjuvant and neoadjuvant settings
  • Today, trastuzumab is regarded as the standard of care for patients with HER-2-positive breast cancer
  • Other agents include:
    • The small-molecule tyrosine kinase inhibitor lapatinib and newer drugs, including pertuzumab, trastuzumab-emtansine, neratinib, and ertumaxomab

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