File:MechanismofactionPertuzumab.png

English: The complementary mechanisms of pertuzumab and trastuzumab. (Left) HER2 receptors on the surface of the HER2-expressing breast cancer cells can dimerize with themselves or with other HER receptors in a ligand-dependent or independent manner, thus activating downstream signalling pathways promoting tumor cell proliferation, survival and invasion. Trastuzumab that binds to the domain IV of HER2, prevents the constitutive activation of HER2 by blocking its ligand-independent dimerization, induces its internalization and degradation, and stimulates the immune system to recognize and eliminate HER2-overexpressing cells. (Middle) However, trastuzumab does not prevent the ligand-induced heterodimerization of the receptor with HER3. Following the heregulin (HRG) binding to HER3, a switch from the closed to the open state is induced, exposing the domain II dimerization arm to allow the formation of a HER2/HER3 heterodimer and intracellular signaling. (Right) Adding pertuzumab to trastuzumab promotes binding of pertuzumab to HER2 domain II and prevents HRG-mediated HER2/HER3 dimerization and signalling.