Figure 1.

I) Toxic effects on the heart are a result of anthracycline's ability to inhibit TOP 2β and generate ROS. Reducing TOP 2β activity in cardiomyocytes leads to DNA intercalation and cardiac DNA damage. The mitochondrial DNA is damaged when ROS are produced in excess (mitochondrial DNA). DOX therapy causes cardiotoxicity, in part due to intracellular Ca and Fe accumulation; II) As HER-2 is overexpressed in breast cancer and is directly responsible for the tumor's growth, trastuzumab encourages its dimerization. Trastuzumab inhibits HER-2 homodimerization and heterodimerization with HER-3, hence preventing cancer cell proliferation (left side). Trastuzumab blocks the action of neuregulin, preventing the protective dimerization of HER-2 and cardiomyocytes, leading to mitochondrial malfunction and promotes cellular damage; III) Ipilimumab, blocks antitumor T cell responses by turning off a negative regulator of T cell activation, and pembrolizumab, an inhibitor of PDL-1, allows infiltrating T cells to do their function once they've cleared the tumor's microenvironment. T-cell responses in the heart and muscle are boosted by ipilimumab and nivolumab also contribute to autoimmune cardiotoxicity.