Cancers, Vol. 11, Pages 571: Chronic Treatment with Multi-Kinase Inhibitors Causes Differential Toxicities on Skeletal and Cardiac Muscles

Cancers, Vol. 11, Pages 571: Chronic Treatment with Multi-Kinase Inhibitors Causes Differential Toxicities on Skeletal and Cardiac Muscles Cancers doi: 10.3390/cancers11040571 Authors: Joshua R. Huot Alyson L. Essex Maya Gutierrez Rafael Barreto Meijing Wang David L. Waning Lilian I. Plotkin Andrea Bonetto Despite recent progress, chemotherapy remains the preferred treatment for cancer. We have shown a link between anticancer drugs and the development of cachexia, i.e., body wasting accompanied by muscle loss. The multi-kinase inhibitors (MKIs) regorafenib and sorafenib, used as second-line treatment for solid tumors, are frequently accompanied by several side effects, including loss of muscle mass and strength. In the present study we aimed to investigate the molecular mechanisms associated with the occurrence of muscle toxicities in in vivo conditions. Hence, we treated 8-week old healthy CD2F1 male mice with MKIs for up to six weeks and observed decreased skeletal and cardiac muscle mass, consistent with muscle weakness. Modulation of ERK1/2 and GSK3β, as well as increased expression of markers of autophagy, previously associated with muscle atrophy conditions, were shown in skeletal muscle upon treatment with either drug. MKIs also promoted cardiac abnormalities consistent with reduced left ventricular mass, internal diameter, posterior wall thickness and stroke volume, despite unchanged overall function. Notably, different signaling pat...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research