Circulating Melanoma Cells in the Diagnosis and Monitoring of Melanoma: An Appraisal of Clinical Potential

Abstract

Circulating melanoma cells (CMC) 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. CMC are then shed off or migrate from the primary tumor and intravasate into the vasculature system. A few CMC 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 CMC in the blood of a melanoma patient can be used for disease staging, predicting metastasis development and for evaluating the efficacy of therapeutic agents. Overall survival and disease-free duration can also be correlated with the presence of CMC. Finally, analysis of CMC for druggable therapeutic gene targets could lead to the development of personalized treatment regimens to prevent metastasis. Thus, the study of CMC shows promise for the detection, staging, and monitoring of disease treatment, as well as determination of prognosis and predicting overall disease free survival. These are the areas reviewed in this article.

Circulating Tumor Cells, DNA, and mRNA: Potential for Clinical Utility in Patients With Melanoma

“…In patients with melanoma, the number of detected CTCs range from 0 to more than 10,000 CTCs per 10 mL of blood [3,15,16]. In the same blood sample, there may be approximately 100 million leukocytes and 50 billion erythrocytes.…”

“…In 2014 alone, more than 600 publications searchable on PubMed described the diversity of CTP-related isolation techniques, proof-of-principle findings, and implications for human disease management and clinical study design. In melanoma, several reviews have been written to summarize the state of the art in CTP detection, isolation, and genetic characterization, yet its potential contributions to precision medicine remain uncertain [1][2][3][4][5][6][7].…”

“…Variation in prognosis and the availability of powerful targeted therapies demands tools to better define risk stratification, inform the optimal timing of therapy initiation, and detect drug resistance. Melanoma's variability in surface marker expression poses a unique biological challenge to reliable detection, thus inspiring great variation in CTC detection methodologies [1][2][3][5][6][7]. On the other hand, well-described, melanoma-specific DNA mutations, such as BRAF (B-Raf proto-oncogene, serine/threonine kinase) mutations, allow for ease in conducting proof-ofconcept studies.…”

Brain infiltration by cancer cells: different roads to the same target?

“…[112] Subsequently, the neutrophil-melanoma cell complex binds to endothelial cells of capillaries to promote brain tissue invasion and metastasis growth.…”

“…[112] Finally, in the brain, astrocytes forming and surrounding the tumoral niche may play a protective role towards the tumor cells growth, including melanoma BM, by priming reactive astrocytosis or protecting tumor cells from cytotoxicity induced by chemotherapeutic drugs. [113] …”