Trastuzumab (anti-HER2 monoclonal antibody) exerts its antitumour effect through which mechanism?

• A Competitive inhibition of EGF binding to the HER2 extracellular domain, blocking dimerisation
• B Antibody-dependent cellular cytotoxicity (ADCC) and inhibition of HER2 ectodomain shedding ✓
• C Internalisation and degradation of HER2 by lysosomal enzymes after receptor crosslinking
• D Recruitment of complement and membrane attack complex formation on HER2-overexpressing cells

Explanation

Trastuzumab binds domain IV of the HER2 extracellular region, preventing cleavage of the extracellular domain (ectodomain shedding) which would generate constitutively active p95-HER2 fragment, and prevents downstream PI3K/AKT and RAS/MAPK signalling. It also recruits NK cells and macrophages via its Fc region, triggering ADCC. Pertuzumab (not trastuzumab) blocks HER2 dimerisation by binding domain II. Complement-dependent cytotoxicity is not the primary mechanism for trastuzumab.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.