Trastuzumab (Herceptin) is used in HER2-positive breast cancer. Its pharmacological mechanisms include:

• A Competitive inhibition of HER2 kinase ATP-binding site as a small molecule TKI
• B Binding to subdomain IV of the HER2 extracellular domain, preventing receptor dimerization, promoting internalization/degradation, and ADCC ✓
• C Blocking PI3K directly, preventing downstream mTOR signaling
• D Binding HER2 intracellular domain and preventing phosphorylation of MAPK

Explanation

Trastuzumab is a humanized IgG1 monoclonal antibody that binds subdomain IV of the HER2 extracellular juxtamembrane domain; this binding prevents cleavage of the extracellular domain (which would generate a constitutively active truncated p95-HER2), disrupts HER2 dimerization with other ErbB family members, promotes receptor internalization and degradation, and recruits immune effectors via ADCC. Lapatinib and neratinib are the small molecule TKIs (option A) targeting HER2 intracellular kinase domain.

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

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