Circulating tumor cells as biomarkers in melanoma: techniques, challenges, and clinical applications

Cutaneous melanoma is a malignant tumor and remains a clinical challenge due to unmet needs in risk stratification, real-time treatment monitoring, and early detection of progression or resistance. Early detection is crucial, as prognosis significantly worsens once metastasis occurs. Liquid biopsy has emerged as a powerful, minimally invasive tool for early diagnosis, real-time disease monitoring, and therapeutic guidance. Among its components, circulating tumor cells (CTCs) are rare yet clinically informative, providing insights into tumor heterogeneity, metastatic potential, and prognosis. Given its high heterogeneity, melanoma could particularly benefit from CTC analysis to inform personalized treatment strategies and improve clinical outcomes. Quantification of melanoma CTCs remains limited by low abundance and heterogeneity, as well as the lack of standardized isolation methods across laboratories. This review summarizes current methods for melanoma CTC detection and isolation. It also explores the clinical significance of melanoma CTCs, addressing the challenges and future opportunities for their implementation in clinical practice.