The last few years have seen an exponential rise in cfDNA and ctDNA analysis, but liquid biopsies aren’t a new phenomenon. Dating back to the early 90s when the first mutations of K-RAS and BRAF were discovered, there have been many debates and discussions around the widespread clinical use and standardisation of liquid biopsies. Nowadays, there are many types of liquid biopsies available including blood, CSF, urine, saliva, and pleural effusion.
Manos Karteris, Professor of Biomedical Sciences at Brunel University of London, mentioned the key advantages of liquid biopsies. For example, liquid biopsies are minimally invasive, low cost, and capable of monitoring tumour evolution making them good prognostic tools. Circulating tumour cells (CTCs) leave the primary tumour sites and contribute to metastatic events. CTCs can be hard to detect when they have low levels, and they can fuse with white blood cells. They also move in clusters making them hard to isolate. Furthermore, it is complicated to capture the efficiency of CTCs.
Karteris’s lab investigated liquid biopsies by enumerating and characterizing CTCs by measuring circulating tumour DNA (ctDNA). CtDNA is posed to be a promising modality, according to Karteris, there has been a rapid increase in clinical trial activity from 160 trials in 2023 year to 700 in 2024. There are companion diagnostic tests for lung, breast, anal and colorectal cancers. However, sensitivity is still an issue: “For example, the amount of circulating tumour DNA you get on the cfDNA sample can be a limiting factor for liquid biopsies and ctDNA testing, it can be as low as 0.01 percent or up to 90%.”
Furthermore, Karteris briefly touched on research on the potential of extracellular vesicles (EVs) and exosomes containing tumour-related biomarkers and their potential as diagnostics. He expressed that the clinical utility of EVs needs further exploration from liquid biopsies and other biofluids.
Karteris pointed out that for clinical trials on CTCs, there is a recurrent pattern, they show initial promise but progression beyond early trial phases is slow. To foster clinical progression, standardisation must become a priority; with many multiple detection platforms but no universal methodology has been established.
