Intracellular Cardiac Signaling Pathways Altered by Cancer Therapies

Recent advancements in targeted and immune-specific cancer therapies have improved patient survivorship. Specifically, tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and chimeric antigen receptor (CAR) T-cell therapies have emerged as efficacious treatments for several cancers, including metastatic renal cell carcinoma (mRCC), hematologic malignancies, and solid cancers, respectively. These therapies are associated with complete and durable responses, but as the population of cancer survivors increases, a myriad of unwanted cardiac adverse effects (AEs) have been recognized. Cardiac AEs may be further compounded by the approval of dual combination therapy including TKIs and ICIs used in kidney and liver cancers which may precipitate additive insults to the myocardium. The most common AEs include hypertension, de novo arrhythmias, myocarditis, and heart failure (HF), which confer significant risk of morbidity and mortality. Therefore, it is important to understand the mechanism by which these drugs lead to cardiac dysfunction. In this chapter, we provide a comprehensive review of the most relevant studies demonstrating the impact of TKIs, ICIs, and CAR T-cell therapies on cardiomyocyte signaling and function. Strategies used to prevent, reduce, and treat cardiac dysfunction associated with these cancer therapies will also be explored.