The MNK1/2-eIF4E Axis as a Potential Therapeutic Target in Melanoma

Abstract

Melanoma is a type of skin cancer that originates in the pigment-producing cells of the body known as melanocytes. Most genetic aberrations in melanoma result in hyperactivation of the mitogen activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways. We and others have shown that a specific protein synthesis pathway known as the MNK1/2-eIF4E axis is often dysregulated in cancer. The MNK1/2-eIF4E axis is a point of convergence for these signaling pathways that are commonly constitutively activated in melanoma. In this review we consider the functional implications of aberrant mRNA translation in melanoma and other malignancies. Moreover, we discuss the consequences of inhibiting the MNK1/2-eIF4E axis on the tumor and tumor-associated cells, and we provide important avenues for the utilization of this treatment modality in combination with other targeted and immune-based therapies. The past decade has seen the increased development of selective inhibitors to block the action of the MNK1/2-eIF4E pathway, which are predicted to be an effective therapy regardless of the melanoma subtype (e.g., cutaneous, acral, and mucosal).