Abstract
Simple SummaryCutaneous Melanoma is a form of skin cancer characterized by an elevated mutational load that favors high spread to distant organs and resistance to therapies. The identification of biomarkers, able to dissect normal and pathogenic biological processes and response to therapeutic intervention, is necessary to describe melanoma as accurately as possible, having a positive impact on early diagnosis, in turn selecting the best therapeutic option. Recently, a great number of new biomarkers were evaluated, in order to identify those patients who may have clinical benefit from a therapeutic choice, particularly for immunotherapy. At present, these new biomarkers wait to be validated before clinical use. Hence, the requirement to look at and periodically update the advances in this field.Cutaneous Melanoma classification is constantly looking for specific and sensitive biomarkers capable of having a positive effect on diagnosis, prognosis and risk assessment, eventually affecting clinical outcome. Classical morphological, immunohistochemical and the well-known BRAF and NRAS genetic biomarkers do not allow the correct categorization of patients, being melanoma conditioned by high genetic heterogeneity. At the same time, classic prognostic methods are unsatisfactory. Therefore, new advances in omics and high-throughput analytical techniques have enabled the identification of numerous possible biomarkers, but their potentiality needs to be validated and standardized in prospective studies. Melanoma is considered an immunogenic tumor, being the first form of cancer to take advantage of the clinical use of the immune-checkpoint blockers. However, as immunotherapy is effective only in a limited number of patients, biomarkers associated with different responses are essential to select the more promising therapeutic approach and maximize clinical benefits. In this review, we summarize the most utilized biomarkers for Cutaneous Melanoma diagnosis, focusing on new prognostic and predictive biomarkers mainly associated with immunotherapy.
Highlights
In the last decade, research in melanoma treatment saw two historical moments, defined in 2011 by the FDA approval of ipilimumab and vemurafenib for BRAF protooncogene (BRAF) mutated metastatic melanoma treatment, and in 2014 by the authorization of pembrolizumab and nivolumab for unresectable and metastatic melanoma
This review provides information on the current landscape of biomarkers for melanoma diagnosis, prognosis and prediction described in the literature, reporting those with the best impact on disease classification
To complete the presentation of biomarkers for melanoma, categorization is essential to define a group of them capable to dissect the impact on tumor biology and disease course and a second group defining tumor response to treatment as well as the improvement in overall survival (OS), disease free survival (DFS) and progression free survival (PFS)
Summary
Research in melanoma treatment saw two historical moments, defined in 2011 by the FDA approval of ipilimumab and vemurafenib for BRAF protooncogene (BRAF) mutated metastatic melanoma treatment, and in 2014 by the authorization of pembrolizumab and nivolumab for unresectable and metastatic melanoma These two different approaches, targeted therapy and immunotherapy, are able to attack the advanced stages of melanoma that, until those dates, accounted for the majority of skin cancer related death, representing less than 5% of all cutaneous malignancies [1]. The American Joint Committee on Cancer (AJCC) has recently revised melanoma classification based on Breslow thickness In this implementation, patients can be stratified in risk category by the TNM (tumor, lymph node, metastasis) system, individuating four stages, stage I–IV, comprising different localizations of the disease with different impact on the overall survive and profound effects on prognosis. Biomarkers predicting clinical benefits are a new scientific challenge and their identification essential for an actual precision medicine
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