Table 2.
Association of Chemotherapy-Induced Endothelial Damage With Cardiovascular Complications
| Chemotherapeutics | Cancer87, 88, 89, 90, 91 | Mechanism55,88, 89, 90, 91, 92, 93, 94 |
|---|---|---|
| Anthracyclines (eg, doxorubicin) | Lung, Hodgkin lymphoma, and breast87 | Production of ROS, which promotes breakdown of DNA strands leading to inhibition of DNA synthesis. This cascade causes cell apoptosis, which contributes to accelerated atherosclerosis. |
| Plant alkaloids (eg, paclitaxel and docetaxel) | Breast, colorectal, cervical, endometrial, head and neck, and lung88 | Inhibition of cell proliferation leading to abnormal microtubules. As the tubulin cytoskeleton maintains the integrity of the endothelial layer, plant alkaloids increase the permeability of blood vessels. Endothelial damage promotes the transmigration of LDL and leukocytes into the subintimal space initiating atheroma formation. |
| Alkylating agents (eg, cisplatin) | Testicular, ovarian, bladder and head and neck, gastrointestinal adenocarcinomas, breast, and head and neck tumors | Attachment to DNA, which disrupts DNA repair and eventually leads to apoptosis. Endothelial damage through direct action and production of ROS, which increases oxidative stress and thrombosis via platelet aggregation. Direct cytotoxic effect on the vascular endothelial layer can lead to coronary vasospasm. This class is also associated with elevated lipid profile. |
| Biological therapies/Immunotherapy) (eg, tyrosine kinase inhibitor, immune checkpoint inhibitors) | Colorectal, cervical, lung, and renal | Inhibition of angiogenesis, regression of already formed tumor blood vessels, and altering of blood supply to the tumor cells. Endothelial dysfunction and damage lead to hypertension, cerebral ischemia, and myocardial infarction and are prothrombotic. |
| Antimetabolites (eg, fluorouracil, capecitabine) | Breast, gastrointestinal, and colorectal | Interference with DNA and RNA synthesis by acting as false metabolites, which then prevent DNA synthesis by integration into the DNA strand or blockade of essential enzymes, leading to apoptosis. |
| Hormonal therapies (eg, GnRH agonist) | Breast and prostate | Effect on lipid profile and acceleration of atherosclerosis from hyperlipidemia, particularly increasing LDL and triglycerides, as well as being proinflammatory. |
DNA = deoxyribonucleic acid; GnRH = gonadotropin-releasing hormone; LDL = low-density lipoprotein; RNA = ribonucleic acid; ROS = reactive oxidative species.