Development of ERK1/2 inhibitors as a therapeutic strategy for tumour with MAPK upstream target mutations.

Longfei Miao, Hongqi Tian

Journal of drug targeting 2020 Feb

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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.

Citation

Longfei Miao, Hongqi Tian. Development of ERK1/2 inhibitors as a therapeutic strategy for tumour with MAPK upstream target mutations. Journal of drug targeting. 2020 Feb;28(2):154-165