A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours

Antitumour efficacy of the selumetinib and trametinib MEK inhibitors in a combined human airway–tumour–stroma lung cancer model

“…Interestingly, the higher efficacy observed for trametinib compared to selumetinib is in agreement with previously reported preclinical data (Gilmartin et al, 2011;Yamaguchi et al, 2011). Moreover, the concentrations of the MEK inhibitors efficient in OCA KRAS mut cultures match to the maximal plasma concentrations measured in clinical trials (21-38 nM for trametinib (Infante et al, 2013) and 1.22 M for selumetinib (Adjei et al, 2008)). …”

MicroRNAs 206 and 21 Cooperate To Promote RAS–Extracellular Signal-Regulated Kinase Signaling by Suppressing the Translation of RASA1 and SPRED1

“…genetic changes in these receptors or the mutational activation of RAS or RAF are rare, these tumors often harbor other genetic alterations that promote RAS-ERK pathway activity (26)(27)(28)(29)(30)(31). Supporting the importance of this signaling, TNBC cells are particularly sensitive to drugs such as MEK or PI 3-kinase inhibitors, and combination therapies have been analyzed in clinical trials (23,24,78,79).…”

PACMEL: A phase 1 dose escalation trial of trametinib (GSK1120212) in combination with paclitaxel

“…Trametinib could be given at the recommended monotherapy dose [31]. Toxicities were generally non-overlapping, reversible and consistent with known side-effect profiles for each drug.…”