Liquid Biopsy in Uveal Melanoma: Are We There Yet?

Abstract

In the era of precision oncology, major strides are being made to use individual tumor information for clinical decision-making. Differing from traditional biopsy methods, the emerging practice of liquid biopsy provides a minimally invasive way of obtaining tumor cells and derived molecules. Liquid biopsy provides a means to detect and monitor disease progression, recurrence, and treatment response in a noninvasive way, and to potentially complement classical biopsy. Uveal melanoma (UM) is a unique malignancy, with diagnosis heavily reliant on imaging, few repeat biopsies, and a high rate of metastasis, which occurs hematogenously and often many years after diagnosis. In this disease setting, a noninvasive biomarker to detect, monitor, and study the disease in real time could lead to better disease understanding and patient care. While advances have been made in the detection of tumor-disseminated components, sensitivity and specificity remain important challenges. Ambiguity remains in how to interpret current findings and in how liquid biopsy can have a place in clinical practice. Related publications in UM are few compared to other cancers, but with further studies we may be able to uncover more about the biology of disseminated molecules and the mechanisms involved in the progression to metastasis.

Anticancer Effects of Mifepristone on Human Uveal Melanoma Cells

“…During cellular death or cancer progression, the release of highly fragmented cfDNA is ampli ed, and can be detected in bodily uids. cfDNA is mainly released through processes of apoptosis, necrosis and cellular secretions, and can inform us of the current state of a tumor or cellular system [49,50]. cfDNA derived from a tumor, also referred to as circulating tumor DNA (ctDNA), can be detected in liquid biopsy such as blood and allow for earlier detection, help classify a lesion, inform on mutational burden, and provide real-time disease monitoring in response to treatment [51][52][53][54].…”

Applying Single-Cell Technology in Uveal Melanomas: Current Trends and Perspectives for Improving Uveal Melanoma Metastasis Surveillance and Tumor Profiling

“…(C) DEParray NXT TM brightfield image demonstrating how single cells can be verified and debris and duplets can be excluded for a higher quality of sampling. added insight with relatively good sensitivity and specificity using ultrasensitive droplet polymerase chain reactions technology (Jin and Burnier, 2020). However, this may change with the application of scRNA and scDNA on CTCs, and this may represent the future applications of single-cell technology in liquid biopsies.…”

“…As the single-cell approaches in UM are only just emerging, the literature base is relatively sparse. Most studies have focused predominantly on CTCs in UM (see in more detail later in 4.2) (Tobal et al, 1993 ; Foss et al, 1995 ; Keilholz et al, 2004 ; Boldin et al, 2005 ; Callejo et al, 2007 ; Schuster et al, 2007 ; Fernandes et al, 2008 ; Ulmer et al, 2008 ; Pinzani et al, 2010 ; Suesskind et al, 2011 ; Torres et al, 2011 ; Bidard et al, 2014 ; Mazzini et al, 2014 ; Tura et al, 2014 , 2016 ; Bande et al, 2015 ; Eide et al, 2015 ; Terai et al, 2015 ; Alix-Panabières and Pantel, 2016 ; Anand et al, 2019 ; Jin and Burnier, 2020 ).…”

“…Liquid biopsies that include the analysis of CTC, circulating tumor DNA, and circulating microRNA have been shown to carry such information that may allow us to understand the CTC genome as they progress according to the disease status. Current studies for the detection of CTCs seem inconsistent and focus on the number of CTCs, whereas circulating tumor DNA has been shown to provide added insight with relatively good sensitivity and specificity using ultrasensitive droplet polymerase chain reactions technology (Jin and Burnier, 2020 ). However, this may change with the application of scRNA and scDNA on CTCs, and this may represent the future applications of single-cell technology in liquid biopsies.…”

What’s in a Name? Large Choroidal Nevus, Small Choroidal Melanoma, or Indeterminate Melanocytic Tumor

“…One caveat is that there have been cases of nonmelanocytic tumors that were incorrectly given diagnosis of melanoma on the basis of their molecular profiles, so cytology should not be entirely abandoned [35]. Liquid biopsies using aqueous, vitreous, or blood samples allow detection of diagnostic mutations without the need for tumor biopsy [36, 37].…”