Trastuzumab (Herceptin) is used in HER2-positive breast cancer. Its primary mechanism of antitumor action is:

• A Direct inhibition of HER2 tyrosine kinase enzymatic activity
• B Binding to HER2 extracellular domain, blocking ligand-independent dimerization and triggering ADCC by NK cells ✓
• C Competitively inhibiting ATP binding to the HER2 intracellular kinase domain
• D Promoting HER2 receptor internalization and lysosomal degradation via Fc receptor-independent pathway

Explanation

Trastuzumab is a humanized monoclonal antibody that binds to subdomain IV of the extracellular domain of HER2. Its mechanisms include: (1) steric inhibition of HER2 receptor dimerization (HER2 acts as a preferred dimerization partner for all ErbB receptors, and dimerization is required for downstream RAS-MAPK and PI3K-Akt signaling); (2) induction of antibody-dependent cellular cytotoxicity (ADCC) by recruiting NK cells via the Fc region; (3) prevention of proteolytic cleavage of the HER2 extracellular domain that generates a constitutively active truncated p95-HER2. Small molecule TKIs (lapatinib, neratinib) directly block the intracellular kinase domain, which is the key mechanistic distinction from 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.