Circulating Melanoma Cells: Scoping the Target

CirCulating MelanoMa Cells Molecular markers have been increasingly applied in cancer to assess metastatic risk and to guide treatment, including in melanoma, where assessment of BRAF mutations in tumor tissues to determine suitability for treatment with vemurafenib is now routine (1). Static assessment of tumor tissues, however, does not indicate whether tumor cells are being shed or whether treatment is reducing metastasis. Because melanoma metastasizes hematogenously, examination of circulating melanoma cells (CMC) is a logical as well as a convenient alternative to the examination of tumor tissues. A reliable assessment of CMC numbers and molecular signatures could have major clinical impact. The failure to demonstrate a survival advantage for adjuvant treatment might be linked to inadequate disease staging and, consequently, inadequate assessment of relapse risk. Because CMC may indicate systemic subclinical disease, their detection and analysis may be useful not only for staging/prognosis but also for assessing response to adjuvant therapy. The discovery of CMC theoretically would also allow for earlier detection of metastasis. This could potentially increase the effectiveness of existing therapies. Serial CMC assessments during treatment may allow for the earlier assessment of response, sparing non-responding patients toxicities. Serial CMC assessments could help determine the mechanisms of resistance and suggest interventions to address them. Furthermore, not all patients with melanoma are candidates for surgery to obtain tissue for analysis of molecular markers, and CMC would provide a liquid biopsy of sum total of tumors at all the sites in the patient.