Abstract

Cutaneous melanoma stands out as a model disease on which to study tumor progression and metastasis for several reasons. If undetected or diagnosed late, melanoma is a highly invasive tumor and almost invariably leads to metastatic spread. It tends to metastasize at a time when the tumor burden is low compared to other cancers, which is evident by the size (thickness) of the primary tumor being measured in millimeters. The fact that the majority of the almost 70,000 new melanomas diagnosed in the United States every year are detected when they are still curable, is presumably largely owed to its prominent site of origin, the skin. As a consequence, tissue from early stages of tumor development is relatively easily available for analysis, allowing for the investigation of the whole spectrum of tumor progression and the metastatic process in humans. It is somewhat surprising that comparative genomic approaches to date have not yet consistently identified gene signatures reflecting genes or gene sets that are associated with metastasis or prognosis of melanoma. Nevertheless, tremendous progress has been made in recent years identifying mechanisms leading to metastasis in melanoma. In this review, we highlight some of the key molecules and pathways that have been discovered as drivers of metastatic progression in this disease.

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