Trastuzumab (Herceptin) is used for HER2-positive breast cancer. Its mechanism of antitumor activity is BEST described as:

• A Inhibits HER2 intracellular tyrosine kinase domain, blocking autophosphorylation directly
• B Binds extracellular domain IV of HER2, preventing receptor dimerization, signaling, and promoting ADCC ✓
• C Blocks EGF ligand from binding HER1, reducing transactivation of HER2
• D Induces HER2 receptor internalization via the ubiquitin-proteasome pathway

Explanation

Trastuzumab is a humanized monoclonal IgG1 antibody that binds to the extracellular subdomain IV (juxtatransmembrane region) of the HER2 receptor. This binding prevents receptor homo- and heterodimerization (required for activation of downstream PI3K/Akt and MAPK pathways), promotes receptor internalization and degradation, and recruits immune effector cells via the Fc region to mediate antibody-dependent cellular cytotoxicity (ADCC). Pertuzumab binds HER2 domain II (blocking heterodimerization specifically). Lapatinib inhibits the intracellular tyrosine kinase domain of both HER1 and HER2. The combination of trastuzumab + pertuzumab is the current standard for HER2+ metastatic breast cancer.

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

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Written and medically reviewed by the StethoPrep medical team.