The MAP kinase-interacting kinases (MNKs) as targets in oncology.

INTRODUCTION: The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are switched on by the oncogenic MAPK (ERK) signalling pathway. They phosphorylate eukaryotic initiation factor (eIF) 4E, a protein which recruits ribosomes to mRNAs and thereby mediates their translation. Importantly, overexpression of eIF4E can transform cells, and its function is controlled by a second oncogenic pathway, mechanistic target of rapamycin complex 1. Areas covered: We have evaluated the literature related to the role of the MNKs in human cancers, including their control by oncogenic signalling pathways; their expression and regulation in cancer cells and preclinical cancer models; and their roles in the proliferation, survival and migration/invasion of cancer cells. We also discuss progress towards generating specific and potent inhibitors of the MNKs and data obtained using such compounds. Expert opinion: The available data indicate that MNKs and/or eIF4E phosphorylation play a role in oncogenic transformation, the progression of at least some tumours and especially in processes related to tumour metastasis. MNKs are clearly druggable targets and, as they are not essential, significant 'side effects' of inhibiting the MNKs are likely to be limited. Further work is required to assess the efficacy of MNK inhibition in tackling tumour development, progression and metastasis.