Dated: Sep 25, 2018
Publication Name: Platelets
Citations : Cobimetinib and trametinib inhibit platelet MEK but do not cause platelet dysfunction
The MEK inhibitors cobimetinib and trametinib are used in combination with BRAF inhibitors to treat metastatic melanoma but increase rates of hemorrhage relative to BRAF inhibitors alone. Platelets express several members of the MAPK signalling cascade including MEK1 and MEK2 and ERK1 and ERK2 but their role in platelet function and haemostasis is ambiguous as previous reports have been contradictory. It is therefore unclear if MEK inhibitors might be causing platelet dysfunction and contributing to increased hemorrhage. In the present study we performed pharmacological characterisation of cobimetinib and trametinib in vitro to investigate potential for MEK inhibitors to cause platelet dysfunction.
Contributors: Amanda J. Unsworth, Alexander P. Bye, Neline Kriek, Tanya Sage, Ashley A. Osborne, Dillon Donaghy & Jonathan M. Gibbins