FIGURE 2.

Potential mechanism of cardiotoxicity induced by anti-ErbB-targeted drugs. Trastuzumab and T-DM1 act on the same epitope of ErbB2, and pertuzumab also acts on similar epitopes. They inhibit ErbB2/4 dimerization induced by NRG1. Lapatinib acts directly on the phosphorylation site of ErbB2. Inhibition of ErbB2 can inhibit STAT3 through MAPK/ERK1/2, leading to mitochondrial dysfunction and promoting cell death. Moreover, Akt expression can decrease iNOS and increase eNOS, which leads to the accumulation of ROS in mitochondria. Moreover, the increase in the Bcl-XS/Bcl-XL ratio directly stimulates caspase 3/9 and promotes cell apoptosis.