New Key Publication: Pharmacological inhibition of MEK1/2 signaling disrupts bile acid metabolism through loss of Shp and enhanced Cyp7a1 expression

Small molecule inhibitors directed against the RAS-MAPK pathway are used to treat various malignancies, but side effects can result in treatment interruption, morbidity, and mortality. We show that short-term MEK inhibition deregulates the expression of genes involved in bile acid metabolism and consequently causes profound alterations in bile acid metabolism. Our work contributes to understanding the initial mechanisms by which RAS MAPK inhibitors can cause gastrointestinal complications, hepatotoxicity, and related side effects.

Authors:

• Cristy R.C. Verzijl

• Ivo P. van de Peppel

• Roos E. Eilers

• Vincent W. Bloks

• Justina C. Wolters

• Martijn Koehorst

• Niels J. Kloosterhuis

• Rick Havinga

• Mathilde Jalving

• Dicky Struik

• Johan W. Jonker

Read more: Biomedicine & Pharmacotherapy: https://www.sciencedirect.com/science/article/pii/S0753332223000586