Molecular and Immune Biomarkers for Cutaneous Melanoma: Current Status and Future Prospects

SIMPLE SUMMARY: The prognosis and treatment of metastatic melanoma have changed substantially since the advent of target therapy and immune checkpoint inhibitors. Thus, strategies must be developed to identify responder patients, reduce toxicities, and investigate target and immune based therapy ideal sequencing. To this aim, the determinants driving response, resistance, and adverse events, should be defined. In addition, novel oncogenic drivers should be discovered to provide new therapeutic targets. Current methods of detection, prognosis and monitoring of melanoma are based on clinical, morphological and histopathologic characteristics of the tumor. This review provides an update on prognostic and predictive biomarkers with a potential application in melanoma patients’ clinical management. ABSTRACT: Advances in the genomic, molecular and immunological make-up of melanoma allowed the development of novel targeted therapy and of immunotherapy, leading to changes in the paradigm of therapeutic interventions and improvement of patients’ overall survival. Nevertheless, the mechanisms regulating either the responsiveness or the resistance of melanoma patients to therapies are still mostly unknown. The development of either the combinations or of the sequential treatment of different agents has been investigated but without a strongly molecularly motivated rationale. The need for robust biomarkers to predict patients’ responsiveness to defined therapies and for their stratification is still unmet. Progress in immunological assays and genomic techniques as long as improvement in designing and performing studies monitoring the expression of these markers along with the evolution of the disease allowed to identify candidate biomarkers. However, none of them achieved a definitive role in predicting patients’ clinical outcomes. Along this line, the cross-talk of melanoma cells with tumor microenvironment plays an important role in the evolution of the disease and needs to be considered in light of the role of predictive biomarkers. The overview of the relationship between the molecular basis of melanoma and targeted therapies is provided in this review, highlighting the benefit for clinical responses and the limitations. Moreover, the role of different candidate biomarkers is described together with the technical approaches for their identification. The provided evidence shows that progress has been achieved in understanding the molecular basis of melanoma and in designing advanced therapeutic strategies. Nevertheless, the molecular determinants of melanoma and their role as biomarkers predicting patients’ responsiveness to therapies warrant further investigation with the vision of developing more effective precision medicine.