What is the mechanism of action of trastuzumab?

• A. HER2 receptor–targeted activity with inhibition of signaling and immune-mediated effects (ADCC)
• B. VEGF inhibition
• C. PD-1 blockade
• D. CD20 targeted depletion

Answer: (A)

Trastuzumab binds the HER2 receptor, which is overexpressed in certain cancers, and works through two main actions. First, it blocks HER2 signaling by preventing receptor activation and dimerization, which dampens downstream pathways like PI3K/AKT and MAPK that drive cell growth and survival. It also promotes internalization and downregulation of HER2 on the cell surface, further reducing signaling.

Second, its antibody structure recruits the immune system to attack the cancer cell. The Fc region engages NK cells and other effector cells, triggering antibody-dependent cellular cytotoxicity (ADCC) to kill the tumor cell.

This dual approach—directly inhibiting HER2-driven signaling and engaging immune-mediated killing—distinguishes trastuzumab from therapies that inhibit VEGF, block PD-1, or deplete CD20.