The Potential Role of Liquid Biopsies in Advancing the Understanding of Neuroendocrine Neoplasms

Abstract

Tumour tissue as a source for molecular profiling and for in vivo models has limitations (e.g., difficult access, limited availability, single time point, potential heterogeneity between primary and metastatic sites). Conversely, liquid biopsies provide an easily accessible approach, enabling timely and longitudinal interrogation of the tumour molecular makeup, with increased ability to capture spatial and temporal intra-tumour heterogeneity compared to tumour tissue. Blood-borne biomarker assays (e.g., circulating tumour cells (CTCs), circulating free/tumour DNA (cf/ctDNA)) pose unique opportunities for aiding in the molecular characterisation and phenotypic subtyping of neuroendocrine neoplasms and will be discussed in this article.

Quantitative Analysis of Plasma Cell-Free DNA and Its DNA Integrity and Hypomethylation Status as Biomarkers for Tumor Burden and Disease Progression in Patients with Metastatic Neuroendocrine Neoplasias

“…In neuroendocrine neoplasias, the vast majority of studies of liquid biopsies so far have focused on the use of circulating tumor cells (CTCs) as a surrogate parameter for tumor burden and as a source for the genomic or molecular profiling of the tumor DNA. Less frequently, circulating free tumor DNA (ctDNA) or RNA has been used for transcript profiling or genomic analysis of the tumors [ 8 ]. However, in contrast to other tumor entities like breast or lung cancer, where analysis of CTCs is already an established tool for the diagnosis and management of the patients, the potential role of liquid biopsies in the management of patients with NEN still needs to be established.…”

“…However, in contrast to other tumor entities like breast or lung cancer, where analysis of CTCs is already an established tool for the diagnosis and management of the patients, the potential role of liquid biopsies in the management of patients with NEN still needs to be established. The major limitations of CTC quantification and the genetic profiling of circulating tumor DNA are the low number and detection rate of TCs and the rarity of targetable alterations in NENs [ 8 ]. Therefore, taking a more general approach with the characterization of the total circulating cell-free DNA plasma concentration and its methylation and fragmentation status may offer a more feasible and comprehensive insight into a patient’s tumor disease and may even provide information about the tumor microenvironment [ 6 ].…”

Genetics-guided therapy in neuroendocrine carcinoma: response to BRAF- and MEK-inhibitors

“…Chae ( 21 ) and Klempner ( 22 ) successfully tracked BRAF -mutation in blood and urine of two NEC-patients. Compared to traditional tissue biopsies, liquid biopsies may provide a more nuanced picture of the disease, while also being less invasive ( 26 – 29 ).…”

Molecular Profiling of Well-Differentiated Neuroendocrine Tumours: The Role of ctDNA in Real-World Practice

“…In addition, it is extremely difficult to make a decision about the right technology to apply (whole-genome, whole-exome or RNA-sequencing) in an extremely volatile context regarding the cost and constant evolution of technology. Cell-free DNA may offer an easily accessible, alternative source of fresh tumour material for genomic characterisation; the profiling of its DNA fraction, namely ctDNA, has proven informative and clinically useful in different cancer types, and may also find application in patients with NENs [ 10 , 11 ]. In addition, ctDNA readouts, if detectable, can be measured over time to monitor changes in tumour burden and genomic profile.…”