Microphthalmia‐associated transcription factor in melanoma development and <scp>MAP</scp>‐kinase pathway targeted therapy

<jats:title>Summary</jats:title><jats:p>Malignant melanoma is a neoplasm of melanocytes, and the microphthalmia‐associated transcription factor (<jats:styled-content style="fixed-case">MITF</jats:styled-content>) is essential for the existence of melanocytes. <jats:styled-content style="fixed-case">MITF</jats:styled-content>'s relevance for this cell lineage is maintained in melanoma, where it is an important regulator of survival and balances melanoma cell proliferation with terminal differentiation (pigmentation). The <jats:italic><jats:styled-content style="fixed-case">MITF</jats:styled-content></jats:italic> gene is amplified in ~20% of melanomas and <jats:styled-content style="fixed-case">MITF</jats:styled-content> mutation can predispose to melanoma development. Furthermore, the regulation of <jats:styled-content style="fixed-case">MITF</jats:styled-content> expression and function is strongly linked to the <jats:styled-content style="fixed-case">BRAF</jats:styled-content>/<jats:styled-content style="fixed-case">MEK</jats:styled-content>/<jats:styled-content style="fixed-case">ERK</jats:styled-content>/<jats:styled-content style="fixed-case">MAP</jats:styled-content>‐kinase (<jats:styled-content style="fixed-case">MAPK</jats:styled-content>) pathway, which is deregulated in >90% of melanomas and central target of current therapies. <jats:styled-content style="fixed-case">MITF</jats:styled-content> expression in melanoma is heterogeneous, and recent findings highlight the relevance of this heterogeneity for the response of melanoma to <jats:styled-content style="fixed-case">MAPK</jats:styled-content> pathway targeting drugs, as well as for <jats:styled-content style="fixed-case">MITF</jats:styled-content>'s role in melanoma progression. This review aims to provide an updated overview on the regulation of <jats:styled-content style="fixed-case">MITF</jats:styled-content> function and plasticity in melanoma with a focus on its link to <jats:styled-content style="fixed-case">MAPK</jats:styled-content> signaling.</jats:p>