A 55-year-old woman with HER2-positive breast cancer receives trastuzumab (Herceptin). Which mechanism of action correctly describes trastuzumab's anti-tumour effect?

• A Blocks HER2 intracellular tyrosine kinase domain, preventing downstream PI3K/AKT signalling
• B Binds domain IV of HER2 extracellular domain, preventing ligand-independent homodimerisation and heterodimerisaton, and inducing antibody-dependent cellular cytotoxicity (ADCC) ✓
• C Delivers a cytotoxic payload (emtansine) directly linked to the antibody for targeted kill
• D Stimulates anti-HER2 CD8+ T-cell responses by acting as an immune checkpoint inhibitor

Explanation

Trastuzumab binds domain IV of HER2's extracellular region, preventing receptor dimerisation and constitutive signalling, inducing receptor internalisation and degradation, and engaging immune effector mechanisms (ADCC via Fc region engagement of NK cells). Lapatinib and neratinib block the intracellular tyrosine kinase domain. Ado-trastuzumab emtansine (T-DM1) delivers emtansine as an antibody-drug conjugate—a different agent. Checkpoint inhibitors act on PD-1/CTLA-4, not HER2.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.