MEK/ERK inhibitors: proof-of-concept studies in lung fibrosis

There is no therapy for chronic fibroproliferative diseases, in spite of the fact that current health statistics suggest that these (which include cardiovascular disease, pulmonary fibrosis, diabetic nephropathy, liver cirrhosis and systemic sclerosis) have been estimated to cause approximately 45% of the deaths in the developed world. Recently, many studies have shown that mitogen activated protein kinases (MAPKs) are activated in response to fibrogenic agents and contribute to the formation and function of the myofibroblast, the critical cell type responsible for excessive scarring. A recent report by Madala and colleagues (Am J Respir Cell Mol Biol, 2011) has provided a proof-of-concept study showing that the specific MEK inhibitor ARRY-142886 (ARRY) can both suppress the progression of fibrosis and reverse an animal model of lung fibrosis. Thus MEK inhibition could be a valuable method to treat lung fibrosis.