Extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylate a variety of substrates that play key roles in promoting cell survival and proliferation. Many inhibitors, acting on upstream of the ERK pathway, exhibit excellent antitumor activity. However, drug-resistant tumour cells invariably emerge after their use due to the reactivation of ERK1/2 signalling. ERK1/2 inhibitors have shown clinical efficacy as a therapeutic strategy for the treatment of tumours with mitogen-activated protein kinase (MAPK) upstream target mutations. These inhibitors may be effective against cancers with altered MAPK upstream pathway and may be used as a possible strategy to overcome acquired resistance to MAPK inhibitors. In this review, we describe the mechanism and types of ERK1/2 inhibitors, summarise the current development status of small-molecule ERK1/2 inhibitors, including the preclinical data and clinical study progress, and discuss the future research directions for the application of ERK1/2 inhibitors.
Keywords: ERK1/2 inhibitors; MAPK pathway; clinical; drug resistant; preclinical; tumour.