Endothelium as a Source of Cardiovascular Toxicity From Antitumor Kinase Inhibitors

Area of Science:

• Oncology
• Cardiology
• Molecular Biology

Background:

• Kinase inhibitors (KIs) are targeted cancer therapies with fewer side effects than chemotherapy.
• Cardiovascular side effects are a significant limitation of many targeted cancer therapies.
• Endothelial cells are crucial for cardiovascular health and are exposed to systemic anticancer drugs.

Purpose of the Study:

• To review the evidence linking kinase inhibitor-induced endothelial cell dysfunction to cardiovascular toxicity.
• To examine specific classes of KIs associated with endothelial toxicity.

Main Methods:

• Literature review of preclinical and clinical studies.
• Analysis of signaling pathways affected by KIs in endothelial cells.
• Examination of cardiovascular toxicities associated with specific KI classes.

Main Results:

• Perturbation of signaling pathways by KIs, both on- and off-target, can lead to endothelial dysfunction.
• Vascular endothelial growth factor inhibitors, BCR-Abl KIs, and Bruton tyrosine inhibitors are associated with endothelial toxicity.
• Emerging data suggests other novel KI classes also pose risks to endothelial cells.

Conclusions:

• Endothelial cell dysfunction is a key mechanism underlying the cardiovascular toxicities of various kinase inhibitors.
• The endothelium is a critical target for preventing and potentially treating cardiovascular complications of targeted cancer therapy.