Recent Developments of Circulating Tumor Cell Analysis for Monitoring Cutaneous Melanoma Patients

Abstract

Circulating tumor cells (CTCs) have been studied using multiple technical approaches for interrogating various cancers, as they allow for the real-time assessment of tumor progression, disease recurrence, treatment response, and tumor molecular profiling without the need for a tumor tissue biopsy. Here, we will review studies from the last 15 years on the assessment of CTCs in cutaneous melanoma patients in relation to different clinical outcomes. The focus will be on CTC detection in blood samples obtained from cutaneous melanoma patients of different clinical stages and treatments utilizing multiple platforms. Assessment of multiple molecular melanoma-associated antigen (MAA) markers by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was the most common assay allowing for the improvement of assay sensitivity, tumor heterogeneity, and to predict patient outcomes. Multicenter studies demonstrate the utility of CTC assays reducing the bias observed in single- center trials. The recent development of CTC enrichment platforms has provided reproducible methods. CTC assessment enables both multiple mRNAs and DNAs genomic aberration profiling. CTC provides specific important translational information on tumor progression, prediction of treatment response, and survival outcomes for cutaneous melanoma patients. The molecular studies on melanoma CTCs have provided and may set standards for other solid tumor CTC analyses.

Metastatic Melanoma: Liquid Biopsy as a New Precision Medicine Approach

“…The detection and isolation methods of CTCs are different but are all essentially based on the physical and biological characteristics of the cells [ 67 ]. The EPithelialImmunoSPOT (EPISPOT) assay (which exploits tumor expression of specific molecules) allows blood detection of even a single cell and has produced significant results in terms of cell concentration assessment in several solid tumors [ 68 , 69 ]. The assay discriminates tumor cells from “normal” cells by selectively recognizing the expression of the epithelial cell adhesion molecule (EpCAM) [ 70 ].…”

Point‐of‐care optical devices in clinical imaging and screening: A review on the state of the art

“…CBC, circulating blood clot; CTC, circulating tumour cell; RBC, red blood cell. Image credits: Adapted from [62], reprinted with permission from the American Association for the Advancement of Science.…”

“…The CTC detection threshold can be improved by evaluating large blood volumes, but collecting blood samples greater than 50 mL in volume is clinically limited [74]. An in vivo liquid biopsy based on photoacoustic flow cytometry‐based technology (Cytophone) was deployed for the non‐invasive, label‐free and sensitive detection of CTCs directly from the bloodstream of melanoma patients [62].…”

Skin Cancer Research Goes Digital: Looking for Biomarkers within the Droplets

“…Besides ctDNA and miRNAs, circulating tumor cell (CTC) characterization via ddPCR may offer novel insights into tumor invasion and therapeutic responses in skin cancer patients. Dissociated from the primary tumors or metastases, CTCs are rare cells present in the blood and lymphatic circulation that allow for both mRNA and DNA genomic profiling [ 181 ]. The identification of a high number of CTCs in patients with solid tumors, including CM and SCC, predicts poor survival, most likely due to CTCs’ ability to act as “seeds” of clinical metastases [ 182 , 183 ].…”

“…However, until recently, the molecular characterization of CTCs seemed very challenging, due to the need for more sensitive methods to detect and quantify the subtle omic alterations present at this level. Nonetheless, the development of ddPCR technology has largely solved this issue, providing reliable translational information on tumor progression, therapeutic responses, and survival outcomes for skin cancer patients and others [ 181 ].…”