Mechanisms and Insights for the Development of Heart Failure Associated with Cancer Therapy

Figures

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  Figure 1. Overview of the interaction between antineoplastic chemotherapy and the role of oxidative stress in development of cardiotoxicity. The cumulative effect of chemotherapeutic agents results in the accumulation of reactive oxygen species and other mediators of oxidative stress, such as free iron, as antioxidants and scavenging enzymes are prevented from maintaining proper balance as they normally do under healthy physiologic conditions.

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  Figure 2. The main immunotherapy approaches that are approved for clinical use in cancer are the immune checkpoint inhibitors. These therapies are monoclonal antibodies that target the CTLA-4 and PD-1 receptors and the PD-1 ligand PD-L1, which are involved in the regulation of T cell activation. (a) T cell activation requires two signals: first, antigen recognition by the T cell receptor (TCR) following antigen presentation by major histocompatibility complex (MHC) class II molecules on the surface of antigen-presenting cells; and, second, signal modulation by CD80 or CD86 binding to the CD28 receptor. CTLA-4 is located on the T cell surface and competes with the CD28 receptor to bind CD80 or CD86, thereby blocking T cell activation. CTLA-4 inhibitors block CTLA-4–CD80 or CTLA-4–CD86 binding to facilitate T cell activation (dashed line). (b) PD-1 is a surface receptor that is expressed by T cells and promotes apoptosis of antigen-specific T cells and reduces apoptosis of regulatory T cells through its interaction with its ligand, PD-L1, which is expressed by tumour cells and myeloid cells. This interaction is useful in preventing autoimmunity in physiological conditions, but cancer cells…