BioProject

BRAF or RAS mutation-induced aberrant activation of the mitogen-activated protein kinase (MAPK) pathway is frequently observed in human cancers. More...

BRAF or RAS mutation-induced aberrant activation of the mitogen-activated protein kinase (MAPK) pathway is frequently observed in human cancers. As the key downstream node of MAPK pathway, ERK1/2 is as an important therapeutic target. GDC-0994 (ravoxertinib), an orally bioavailable, highly selective small-molecule inhibitor of ERK1/2, showed acceptable safety and pharmacodynamic profile in a recent phase I clinical trial. In this study, we investigated dependence of the anti-tumor effect of ERK inhibitor GDC-0994 on genetic alterations in the MAPK pathway. Our date showed that the expression of a large number of genes, particularly the genes in the cell cycle pathway, were significantly changed after GDC-0994 treatment in BRAF mutant cells, while no remarkable expression change of such genes was observed in wild-type cells. Overall design: To investigate the mechanism of the anti-tumor effect of ERK inhibitor GDC-0994, we selected the BRAF mutant cell KHM-5M and the BRAF wild-type cell TTA-1 as the research objects. These two cells were treated with vehicle (DMSO) or 1μM of GDC-0994 for 24 h in triplicate. RNA-seq was then performed and analyzed. Less...