Jensen and colleagues identify underlying causes of cardiotoxicity of new therapies used to treat cancers

TraCS-funded research:

Brian Jensen, MD, associate professor of medicine and pharmacology, and colleagues identified for the first-time mechanisms underlying the cardiotoxicity of kinase inhibitors used to treat cancer.

In their work published in the Journal of the American Heart Association (Early View), they identified STAT and EGFR inhibition using kinome and transcriptome profiling in preclinical studies replicating the cardiotoxicity seen in patients receiving sorafenib and sunitinib (cardiotoxic multitargeted kinase inhibitors). They also identify that cardio-safe erlotinib (epidermal growth factor receptor inhibitor) may result from upregulation of the cardioprotective Stat3 (signal transducer and activator of transcription 3) pathway. The study was co-authored by UNC colleagues Timothy J. Stuhlmiller, Jon S. Zawistowski, Xin Chen, Noah Sciaky, Steven P. Angus, Sean T. Hicks, Traci L. Parry, Wei Huang, Ju Youn Beak, Monte S. Willis, and Gary L. Johnson.

Link to full article "Kinome and transcriptome profiling reveal broad and distinct activities of erlotinib, sunitinib, and sorafenib in the mouse heart and suggest cardiotoxicity from combined STAT and EGFR inhibition":
jaha.ahajournals.org/content/6/10/e006635/tab-e-letters