Liquid Biopsies

Liquid biopsies are minimally invasive tests that analyse tumour-derived material circulating in bodily fluids, most commonly blood, but also urine, cerebrospinal fluid and other compartments. Key targets include circulating tumour DNA (ctDNA), released by apoptotic or necrotic tumour cells; circulating tumour cells (CTCs), intact malignant cells shed into the bloodstream; and extracellular vesicles (EVs), lipid-bound nanoparticles carrying proteins, RNA and DNA. Modern sequencing technologies—ranging from digital PCR and targeted NGS panels to untargeted whole-genome approaches—enable detection of low-frequency mutations, copy-number changes and epigenetic markers. Liquid biopsies facilitate early cancer detection, guide therapy selection by revealing actionable mutations, monitor minimal residual disease post-treatment, track the emergence of resistance mechanisms and inform prognosis. Their non-invasive nature supports serial sampling, offering a dynamic portrait of tumour evolution that overcomes limitations of single tissue biopsies. As assays gain sensitivity and standardisation, liquid biopsies are poised to transform oncology practice worldwide, broadening access to molecular diagnosis and personalised treatment in settings where repeat biopsies may be impractical or unsafe.

Research from Nature Portfolio

Studies have standardised droplet digital PCR assays for paediatric diffuse midline glioma, optimising primer design and pre-amplification to achieve consistent detection of H3K27M mutations in cerebrospinal fluid and plasma, with 100 % sensitivity and specificity across multiple centres. In another report, ctDNA from paediatric medulloblastoma patients was shown to recapitulate subgroup-specific alterations and subclonal diversity, with longitudinal sampling enabling the tracking of minimal residual disease and clonal evolution at relapse. Further research in hepatocellular carcinoma has demonstrated that a single nucleotide variant in MLH1 detected in plasma ctDNA, combined with quantification of total ctDNA levels, predicts overall survival more accurately than ctDNA abundance alone, underscoring the prognostic value of mutation-specific liquid biopsy assays.

Liquid Biopsies publication trend

The graph below shows the total number of articles in liquid biopsies across all publications each year (not limited to Nature Index journals).

Technical terms

Circulating tumour DNA (ctDNA): Fragments of DNA released into body fluids by tumour cells, harbouring somatic mutations and epigenetic alterations.

Circulating tumour cell (CTC): An intact cancer cell that has detached from a primary or metastatic lesion and entered the circulation.

Extracellular vesicle (EV): A membrane-bound nanoparticle secreted by cells, carrying proteins, lipids and nucleic acids that reflect the phenotype of the cell of origin.

Droplet digital PCR (ddPCR): A sensitive technique for quantifying low-abundance DNA variants by partitioning a sample into thousands of droplets for individual PCR reactions.

Next-generation sequencing (NGS): High-throughput sequencing platforms that enable parallel analysis of multiple genomic regions for mutations, copy-number changes and structural variants.

Minimal residual disease (MRD): A small population of cancer cells that persists after therapy, detectable by ultra-sensitive liquid biopsy assays and predictive of relapse.

References

1. Standardization of the liquid biopsy for pediatric diffuse midline glioma using ddPCR. Scientific Reports (2021).
2. Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma. Nature Communications (2020).
3. MLH1 single-nucleotide variant in circulating tumor DNA predicts overall survival of patients with hepatocellular carcinoma. Scientific Reports (2020).
4. Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid. Cell Reports Medicine (2023).
5. DNA methylation drives a new path in gastric cancer early detection: Current impact and prospects. Genes & Diseases (2023).
6. Liquid biopsy in gastric cancer: predictive and prognostic biomarkers. Cell Death & Disease (2022).
7. Circulating small extracellular vesicle-derived splicing factor 3b subunit 4 as a non-invasive diagnostic biomarker of early hepatocellular carcinoma. Journal of Experimental & Clinical Cancer Research (2023).