MYC as a key target for melanoma therapy.

Melanoma, the most aggressive form of skin cancer, arises from malignantly transformed melanocytes. Its incidence and mortality are increasing despite the enormous advances in both the knowledge of the disease and the development of effective therapies. From a genetic point of view, cutaneous melanoma can be classified as driven by mutations in BRAF, NRAS or NF1, or the absence of these mutations (triple wildtype). MYC, an oncogene deregulated in most human cancers, drives tumor progression by exerting a broad array of functions that affect all the hallmarks of cancer. In this context, increased MYC activity in melanoma patients occurs by amplification of its gene locus, or by upstream signaling leading to its stabilization and overexpression. In this review, we discuss the role of MYC in melanoma, its relationship with the response and resistance to both targeted therapies and immunotherapy, the different approaches that have been tested to target MYC in this disease, and finally, the future directions towards MYC becoming a target in melanoma.