Dear Colleagues, 

Before the recent advances in the treatment landscape of metastatic melanoma, disease outcomes were poor, with a median overall survival of approximately 6 months and 5-year survival rate of ~5–7%. Two therapeutic strategies have paved the way toward substantially improving the overall response rate and melanoma-specific survival: i) the modulation of the immune system with monoclonal antibodies acting as immune-checkpoint inhibitors (ICIs), targeting either the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) or the programmed cell-death 1 (PD-1); and ii) BRAF and MEK inhibitors that target the mitogen-activated protein kinase (MAPK) pathway, which is constitutively active in melanoma harboring BRAF V600 mutations.

Both ICIs and BRAF/MEKi combinations are recommended as 1st- or 2nd-line therapies for advanced melanoma as well as in adjuvant settings. Nevertheless, both strategies are expensive, and their long-term benefit is limited to a subgroup of patients.

With regard to BRAF/MEK, PFS and OS are approximately 12–14 months and 24–33 months, respectively, reflecting the development of resistance mechanisms in the majority of patients. From a molecular point of view, acquired resistance is related to a reactivation of the MAPK pathway. From a clinical point of view, on the other hand, a pooled analysis helped to identify routinely used clinical parameters as predictors of outcome in patients treated with BRAFi and MEKi in the context of clinical trials. Similarly, although single-agent anti-PD-1/PD-L1 therapy has demonstrated promising clinical activity in a large proportion of metastatic melanoma patients, primary and acquired resistance to immunotherapies can develop—and in the adjuvant setting, 30% of patients receiving anti PD-1 therapy still relapse. Pursuing treatment strategies to overcome primary and acquired resistance is thus important in order to further improve patients’ outcome. Moreover, there is an increasing need for biomarkers helping in the selection of patients who can achieve long-term benefits from the proper selection of therapeutic strategy, as well as for the possible prediction of adverse events related to immunotherapy and targeted therapy.

In this Special Issue, we will collect high-quality original articles as well as authoritative review papers summarizing new, exciting data or strong overviews of biomarkers in melanoma patients, both in early and advanced disease. This Special Issue will help clinicians, scientists, and translational researchers to identify the most promising biomarkers in melanoma. This could ultimately help us to develop combination treatment strategies in melanoma based on a solid translational basic and clinical background.

Prof. Dr. Piotr L. Rutkowski
Prof. Dr. Mario Mandalà
Guest Editors

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