Melanoma is an aggressive form of skin cancer characterized by poor prognosis and high mortality. The
development of targeted agents based on the discovery of driver mutations as well as the implementation of
checkpoint inhibitor-based immunotherapy represents a major breakthrough in the treatment of metastatic
melanoma. However, in both cases the development of drug resistance and immune escape mechanisms as well as
the lack of predictive biomarkers limits their extraordinary clinical efficacy. In this article, we summarize the
available therapeutic options for patients with metastatic melanoma, outline the mechanisms implicated in the
resistance to both targeted agents and immunotherapy, discuss potential predictive biomarkers and outline future
therapeutic approaches under investigation.
Keywords: Melanoma, targeted therapy, immunotherapy, immune checkpoint molecules, PD-1, PD-L1, BRAF inhibitor resistance,
immunotherapy resistance, predictive biomarkers.
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