Cardiovascular Complications of Pan-Cancer Therapies: The Need for Cardio-Oncology

Figures

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  Figure 1. Schematic diagram of the mechanisms of VEGF (receptor) inhibitors-induced cardiovascular complications. Inhibiting the PI3K/Akt pathway causes apoptosis to be activated and ROS to accumulate, which may harm mitochondrial function. Whereas, blocking off-target kinases such as AMPK is linked to disrupting energy homeostasis, decreased cell survival, and a reduced ability to respond to cardiac stress. Each element might have an impact on how HF develops. When it comes to artery thrombosis, the lowered level of PGI2 and NO encourages platelet aggregation, and the level of TXA2 is elevated, which predisposes an individual to ATEs. Furthermore, oxidative stress may result from reduced NO production. Additionally, compromised vascular integrity could root in antiangiogenesis and lead to thrombosis. To sum up, hypertension, cardiac dysfunction, and ATEs are brought on by VEGF (receptor) suppression. AMPK, adenosine 5′-monophosphate-activated protein kinase; ATE, arterial thromboembolic event; NO, nitric oxide; PGI2, prostacyclin; ROS, reactive oxygen species; TKIs, tyrosine kinase inhibitors; TXA2, thromboxane A2; VEGF, vascular endothelial growth factor.

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  Figure 2. The primary mechanisms of ICIs-associated cardiotoxicity. Surface MHCs and co-inhibitory molecules including B7 or PD-1 ligands on tumor cells as well as APC (e.g., dendritic cells) attach to activated T cells through the TCR, PD-1, and CTLA-4 receptors. Apoptosis of tumor cells induced by ICI is mediated by the activation of T cells. The PD-L1 ligands on cardiomyocytes are hypothesized to be responsible for downregulating this pathway in the myocardium. Myocarditis and atherosclerosis are the primary outcomes of blocking this regulatory pathway. APC, antigen-presenting cell; CTLA-4, cytotoxic T lymphocyte-associated protein-4; MHC, major histocompatibility complex; PD-1, programmed cell death 1; PD-L1, programmed death ligand 1; TCR, T-cell receptor. Figure 2 was modified from Servier Medical Art (http://smart.servier.com/ (accessed on 30 March 2023)), licensed under a Creative Common Attribution 3.0 Generic License (https://creativecommons.org/licenses/by/3.0/ (accessed on 30 March 2023)).

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  Figure 3. An overview of cardiovascular complications caused by various cancer therapies. There exists a plethora of acknowledged cardiovascular side effects associated with cancer treatments. Pan-cancer therapies encompass a range of treatments, including classic chemotherapeutic agents, targeted drugs, immuno-oncology agents, and radiotherapy, each impacting various aspects of the cardiovascular system through distinct mechanisms. CAR, chimeric antigen receptor; Her-2, human epidermal growth factor receptor-2; HF, heart failure; ICI, immune checkpoint inhibitor; LV, left ventricular; MI, myocardial infarction; TKI, tyrosine kinase inhibitor; VEGF, epithelial growth factor receptor.