Anthrax lethal toxin-sensitive melanoma cell lines and normal cells had higher phospho-MEK1/2 levels than anthrax lethal toxin-resistant melanoma cell lines and normal tissue types.
Biomarker results from a phase II study of MEK1/2 inhibitor binimetinib (MEK162) in patients with advanced <i>NRAS</i>- or <i>BRAF</i>-mutated melanoma.
Consistent with these observations, pharmacological inhibition of BRAF(V600E) or MEK1/2 in human melanoma cells (using PLX4720 and CI-1040 respectively) led to a striking elevation of BIM expression.
Furthermore, recently identified ERK1/2-inducing mutations in MEK1 and MEK2 (MEK1/2) MAPK genes in melanoma confer resistance to emerging therapeutic MEK inhibitors, underscoring the challenges facing direct kinase inhibition in cancer.
Furthermore, we found that melanoma cell integrin alphav was required for MAPK kinase (MEK) 1 and extracellular signal-regulated kinase (ERK)1/2 activity in 3D-collagen, whereas inhibition of MEK1 activity induced apoptosis.
In patients with BRAF-mutated melanoma specific inhibitors of BRAF<sup>V600E</sup> and MEK1/2 frequently induce initial tumor reduction, frequently followed by relapse.
In recent years, intracellular signal transduction via RAS-RAF-MEK-ERK has been successfully targeted in new treatment approaches for melanoma using small molecule inhibitors against activated BRAF (V600E mutation) and activated MEK1/2.
It inhibited colorectal cancer and melanoma cell proliferation much more effectively than its negative control MS432N (<b>24</b>), and its effect was phenocopied by MEK1/2 knockdown.