MEK inhibitor resistance mechanisms and recent developments in combination trials

The mitogen-activated protein kinase (MAPK) pathway plays a vital role in cellular processes such as gene expression, cell proliferation, survival, and apoptosis. Also known the RAS-RAF-MEK-ERK pathway, MAPK has been implicated approximately one-third of all cancers. Mutations RAS or RAF genes KRAS BRAF are common, these mutations typically promote malignancies by over-activating MEK ERK downstream, which drives sustained proliferation uninhibited growth. Development drugs targeting this research area great interest, especially inhibition MEK. In vitro clinical studies have shown promise for certain inhibitors (MEKi) , MEKi become first treatment option Despite promising results, not patients response to MEKi, mechanisms resistance arise who do positive initial response. This paper summarizes recent developments regarding adaptive potential solutions issue resistance.