Kinase inhibitors can cause endothelial dysfunction through on- and off-target perturbation of signaling pathways, resulting in cardiovascular toxicity.
Do antitumor kinase inhibitors cause cardiovascular toxicity via endothelial dysfunction?
Endothelial dysfunction is a central mechanism underlying the cardiovascular toxicity of various antitumor kinase inhibitors, making the endothelium a potential therapeutic target for prevention.
Kinase inhibitors (KIs) targeting oncogenic molecular pathways have revolutionized cancer therapy. By directly targeting specific tumor-driving kinases, targeted therapies have fewer side effects compared with chemotherapy. Despite the enhanced specificity, cardiovascular side effects have emerged with many targeted cancer therapies that limit long-term outcomes in patients with cancer. Endothelial cells lining all blood vessels are critical to cardiovascular health and are also exposed to circulating levels of systemic anticancer therapies. Both on- and off-target perturbation of signaling pathways from KIs can cause endothelial dysfunction, resulting in cardiovascular toxicity. As such, the endothelium is a potential source, and also a therapeutic target for prevention, of cardiovascular toxicity. In this review, we examine the evidence for KI-induced endothelial cell dysfunction as a mechanism for the cardiovascular toxicities of vascular endothelial growth factor inhibitors, BCR-Abl (breakpoint cluster region-Abelson proto-oncogene) KIs, Bruton tyrosine inhibitors, and emerging information regarding endothelial toxicity of newer classes of KIs.
Travers et al. (Thu,) conducted a review in Cardiovascular toxicity from antitumor kinase inhibitors. Kinase inhibitors was evaluated on Cardiovascular toxicity and endothelial cell dysfunction. Kinase inhibitors can cause endothelial dysfunction through on- and off-target perturbation of signaling pathways, resulting in cardiovascular toxicity.