Table 1.
Vascular damages and diseases induced by the widely prescribed anticancer drugs.
| Anti-cancer drugs and their use in type of cancers | Vascular toxicity | Mechanism | Ref. |
|---|---|---|---|
| Anthracyclines (Doxorubicin)Leukemia, lymphoma, melanoma, uterine, breast, and gastric cancers | * Vascular injury * Microvascular rarefaction * Endothelial dysfunction and hypertension * Hypercoagulation, thrombosis, & atherosclerosis |
* Oxidative stress-mediated ROS accumulation * Apoptosis due to DNA interference * Disruption of the tight junction protein ZO-1 in ECs * Anti-angiogenesis * Mitochondrial DNA damage * The endothelium-based protein C anticoagulant pathway interruption |
(18) (21) (22) (5) (49) (59) |
| Tyrosine kinase inhibitors (TKI) and VEGF inhibitors (VEGFis)Renal cell cancer, gastro-intestinal stromal tumors, hepatocellular cancer | * Microvascular rarefaction * Hypertension * Anti-platelet activity * Hypercoagulation & thrombosis, & atherosclerosis |
* NRF2 downregulation * Anti-VEGF effect, ROS accumulation and disruption of NO levels and PI3K/Akt survival pathway. * Increased vasoconstriction due to disruption of both endothelium-dependent and -independent vasodilatation * Loss of pericytes due to inhibition of PDGF * Increased hematocrit and thrombogenesis activity by reducing NO- and PGI2-mediated anti-platelet activity * Atherosclerosis and increase in the risk of cholesterol embolization syndrome |
(26) (28) (31) (40) (30) (56) (60) |
| CyclophosphamideBreast cancer, lymphoid, and pediatric malignancies | * Vascular injury * Microvascular rarefaction * Hypercoagulation, thrombosis, & atherosclerosis |
* Increased levels of the expression of tissue necrosis factor * Reduced levels of VEGFs * Activation of platelet factor 4 (PF-4) |
(24) (33) (24) |
| CisplatinOvaries, testis cancers, solid tumors of the head and neck | * Vascular injury * Microvascular rarefaction * Endothelial dysfunction and hypertension * Hypercoagulation, thrombosis, & atherosclerosis |
* Increased levels of EC- inflammatory substances to produce hydrogen peroxide * Increased platelet aggregation levels via the arachidonic acid pathway |
(26) (34, 35) (51) |
| 5-Fluorouracil (5-FU)Breast cancer, head and neck cancers, anal, stomach, colon cancers some skin cancers | * Vascular injury * Hypercoagulation, thrombosis, & atherosclerosis |
* Ultrastructural changes in the endothelium of the heart * EC damage * Direct prothrombotic effect |
(27) (65, 66) |
| TaxanesBreast, ovarian, lung, bladder, prostate, melanoma, esophageal, other types of solid tumor cancers | * Microvascular rarefaction | * Endothelial damage and impaired angiogenesis | (37) |