MEK inhibition and immune responses in advanced melanoma

Reinhard Dummer; Egle Ramelyte; Sabrina Schindler; Olaf Thürigen; Mitchell P Levesque; Peter Koelblinger

doi:10.1080/2162402X.2017.1335843

MEK inhibition and immune responses in advanced melanoma

Oncoimmunology. 2017 Aug 10;6(8):e1335843. doi: 10.1080/2162402X.2017.1335843. eCollection 2017.

Authors

Reinhard Dummer¹, Egle Ramelyte¹, Sabrina Schindler¹, Olaf Thürigen², Mitchell P Levesque¹, Peter Koelblinger^{1

3}

Affiliations

¹ University Hospital Zurich, Department Dermatology, Zürich, Switzerland.
² Pierre Fabre Pharma GmbH, Freiburg, Deutschland.
³ Paracelsus Medical University, Department of Dermatology, Salzburg, Austria.

Abstract

phase II and III clinical trials demonstrated modest anti- tumor activity of Binimetinib (MEK162) - a potent allosteric inhibitor of MEK1 and MEK2- in patients with advanced NRAS mutant melanoma. The analysis of the NEMO study in NRAS mutated melanoma, has shown that pre-treatment with immunotherapy improved the outcome of binimetinib therapy. We discuss this finding in the context of in vitro and in vivo effects of MEK inhibition on immuno-critical pathways and interactions.

Keywords: BRAF mutation; MEK inhibitors; MEK kinase pathway; Melanoma; NRAS mutation; immunogenicity; immunotherapy.

Publication types

Review
Research Support, Non-U.S. Gov't