The mitogen-activated protein kinase (MEK MAPK/ERK kinase) signaling pathways play a critical role in the regulation of diverse cellular activities, including survival, differentiation, proliferation, motility, and angiogenesis. Therefore, MEK inhibition was recognized as a promising target for antineoplastic therapy. Trametinib (GSK1120212), an oral MEK inhibitor which is selective for MEK1 and MEK2, has been approved by the FDA for the treatment of metastatic melanoma in a combination with a BRAF inhibitor. In this overview, preclinical and clinical data for trametinib are presented including mechanisms based on in vitro studies as well as findings from different clinical studies. The future clinical trial in different solid tumor entities will define the therapeutic role of this targeted therapy approach, possibly as a combination with other targeted therapies such as BRAF inhibitors.
Keywords: Kinase inhibition; MAPK/ERK Kinase (MEK); Small molecules; Trametinib.