Tyler C Beck, Dimitrios C Arhontoulis, Jordan E Morningstar, Nathaniel Hyams, Andrew Stoddard, Kendra Springs, Rupak Mukherjee, Kris Helke, Lilong Guo, Kelsey Moore, Cortney Gensemer, Rachel Biggs, Taylor Petrucci, Jennie Kwon, Kristina Stayer, Natalie Koren, Andrew Harvey, Heather Holman, Jaclyn Dunne, Diana Fulmer, Ayesha Vohra, Le Mai, Sarah Dooley, Julianna Weninger, Silvia Vaena, Martin Romeo, Robin C Muise-Helmericks, Ying Mei, Russell A Norris
BACKGROUND: Trametinib is a MEK1 (mitogen-activated extracellular signal-related kinase kinase 1) inhibitor used in the treatment of BRAF (rapid accelerated fibrosarcoma B-type)-mutated metastatic melanoma. Roughly 11% of patients develop cardiomyopathy following long-term trametinib exposure. Although described clinically, the molecular landscape of trametinib cardiotoxicity has not been characterized. OBJECTIVES: The aim of this study was to test the hypothesis that trametinib promotes widespread transcriptomic and cellular changes consistent with oxidative stress and impairs cardiac function...
November 2022: JACC CardioOncology