Circulating melanoma cells in the diagnosis and monitoring of melanoma: An appraisal of clinical potential

Circulating melanoma cells (CMCs) are thought to be the foundation for metastatic disease, which makes this cancer especially lethal. Cancer cells contained in the primary tumor undergo genotypic and phenotypic changes leading to an epithelial-to-mesenchymal transition, during which numerous changes occur in signaling pathways and proteins in the cells. CMCs are then shed off or migrate from the primary tumor and intravasate the vasculature system. A few CMCs are able to survive in the circulation through expression of a variety of genes and also by evading immune system recognition to establish metastases at distant sites after extravasating from the vessels. The presence of CMCs in the blood of a melanoma patient can be used for disease staging, predicting metastasis development, and evaluating the efficacy of therapeutic agents. Overall survival and disease-free duration can also be correlated with the presence of CMCs. Finally, analysis of CMCs for druggable therapeutic gene targets could lead to the development of personalized treatment regimens to prevent metastasis. Thus, the study of CMCs shows promise for the detection, staging, and monitoring of disease treatment, as well as for determination of prognosis and predicting overall disease-free survival. These are the areas reviewed in this article.