Cancers and cardiovascular disease continue to be leading causes of
mortality worldwide despite unrelenting efforts to improve therapeutic strategies in
both. Ironically, cardiac adverse effects of anticancer drugs result in an ever-increasing
proportion of deaths in cancer survivors. Doxorubicin, one of the earliest anthracycline
chemotherapeutic agents which has been in clinical use since the 1970s, is notorious
for causing cumulative dose-dependent irreversible cardiac damage, traditionally
termed “type I” cancer therapy-related cardiotoxicity. In the late 1990s, the approval of
trastuzumab, a monoclonal antibody against the human epidermal growth factor
receptor 2 (HER2), initiated an era of targeted anticancer therapy with the hope of
eradicating off-target adverse effects. Unfortunately, trastuzumab treatment leads to the
distinctive “type II” cancer therapy-related cardiotoxicity. As an acknowledged type I
and type II cardiotoxic anticancer agents, doxorubicin and trastuzumab have been
intensely investigated with regard to the complex mechanisms of their effects on the
heart, yet complete understanding remains elusive. This chapter comprehensively
summarizes current mechanistic insights regarding the cardiotoxicity of doxorubicin
and trastuzumab, encompassing the pathophysiology of contractile dysfunction
(cardiomyopathy) and electrical disturbance (arrhythmia). Gaps in knowledge and
recommendations for future advances are also discussed to encourage further
investigation in the field, with the ultimate goal being the effective prevention and/or
treatment of cancer therapy-induced cardiac complications.
Keywords: Arrhythmia, Cancer, Cardiotoxicity, Cardio-oncology, Chemotherapy, Doxorubicin, HER2, Heart failure, Trastuzumab, Targeted therapy.
