Key result
Kinase inhibitors drive cardiovascular toxicities primarily through on- and off-target endothelial dysfunction.
Why the study?
Cardiovascular side effects have emerged with targeted cancer therapies that limit long-term outcomes, with kinase inhibitor-induced endothelial dysfunction serving as a potential mechanism and therapeutic target.
Do antitumor kinase inhibitors cause cardiovascular toxicity via endothelial cell dysfunction in patients with cancer?
Do antitumor kinase inhibitors cause cardiovascular toxicity via endothelial cell dysfunction in patients with cancer?
Cardiovascular toxicities from antitumor kinase inhibitors, including hypertension and arterial thrombosis, are heavily driven by both on- and off-target induction of endothelial cell dysfunction.
Kinase inhibitor cardiotoxicity may be mediated by endothelial dysfunction; hypothesis-generating and requires prospective validation before clinical adoption.
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.
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Travers et al. (2024) conducted a review in Cardiovascular toxicity from antitumor kinase inhibitors. Antitumor kinase inhibitors was evaluated. On- and off-target perturbation of signaling pathways from kinase inhibitors causes endothelial dysfunction, which acts as a key mechanism for subsequent cardiovascular toxicities.
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