Combined targeting of MEK and the glucocorticoid receptor for the treatment of RAS-mutant multiple myeloma.

ABSTRACT:

Background

Multiple myeloma (MM) remains incurable despite recent therapeutic advances. RAS mutations are frequently associated with relapsed/refractory disease. Efforts to target the mitogen-activated protein kinase (MAPK) pathway with the MEK inhibitor, trametinib (Tra) have been limited by toxicities and the development of resistance. Dexamethasone (Dex) is a corticosteroid commonly used in clinical practice, to enhance efficacy of anti-myeloma therapy. Therefore, we hypothesised that the combination of Tra and Dex would yield synergistic activity in RAS-mutant MM.

Methods

The response of human MM cell lines to drug treatment was analysed using cell proliferation assays, Western blotting, Annexin V and propidium iodide staining by flow cytometry and reverse phase protein

SUBMITTER: Sriskandarajah P 

PROVIDER: S-EPMC7106683 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature