Cellular and Molecular Mechanisms of MEK1 Inhibitor-Induced Cardiotoxicity.

ABSTRACT:

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.

Methods

Mice were treated with trametinib (1 mg/kg/d). Echocardiography was performed pre- and post-treatment. Gross, histopathologic, and biochemical assessments were performed

SUBMITTER: Beck TC 

PROVIDER: S-EPMC9700254 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature