Researchers link PLK1 inhibition to CV risks

In a paper published in Nature Medicine, researchers at the Spanish National Cancer Research Centre (CNIO) identified an unexpected cardiovascular risk in mice with polo-like kinase 1 (PLK1) inhibition, including mice treated with volasertib (BI 6727). Boehringer Ingelheim GmbH (Ingelheim, Germany) discontinued that PLK1 inhibitor's development in February 2015, spokesperson Susan Holz told BioCentury.

The researchers found that partial knockout of PLK1 led to arterial structural alterations, which caused aortic rupture and death due to hemorrhaging in half of the treated mice. Specific ablation of PLK1 in vascular smooth muscle cells led to reduced arterial elasticity, hypotension, and an impaired arterial response to angiotensin II-induced hypertension. In mice, administration of 15 mg/kg of volasertib for eight weeks led to defective aortic elasticity, altered responses to angiotensin II, and increased risk of aneurysm and aortic rupture...