Figure 5. Cardiotoxicity by trastuzumab.

Trastuzumab acts on HER2, decreasing signaling via the MEK/ERK pathway and causing apoptosis. It also downregulates the antiapoptotic protein BCL-XL and upregulates the proapoptotic protein BCL-XS; impairs the PI3K/mTOR pathway, causing decrease in autophagy and protein synthesis; and decreases the MAPK activity, dampening protein synthesis. Together, these impairments are cardiotoxic

HER2: human epidermal growth factor 2; BCL-XL: B-cell lymphoma-extra large; BCL-XS: B-cell lymphoma-extra small; PIP2: phosphorylate phosphatidylinositol 4,5 bisphosphate; PIP3: phosphatidylinositol 3,4,4-triphosphate; MAPK: mitogen-activated protein kinase; mTOR: mammalian target of rapamycin