Circulating Nucleic Acids in Oncology

Circulating nucleic acids have emerged as transformative biomarkers in cancer management, offering a non-invasive window into tumour biology. Cell-free DNA (cfDNA) and cell-free RNA (cfRNA) released into the bloodstream reflect processes such as apoptosis, necrosis and active secretion. A subset known as circulating tumour DNA (ctDNA) carries tumour-specific genetic and epigenetic alterations, while circulating tumour RNA (ctRNA) may inform on gene expression and fusion events. Advances in ultrasensitive detection—ranging from targeted PCR assays to next-generation sequencing of broad panels—enable quantification of minimal residual disease, early relapse detection and monitoring of therapeutic response. Epigenetic profiling of methylation signatures further permits inference of tissue of origin. Together, these approaches extend beyond the limits of imaging and tissue biopsy, offering dynamic insights into clonal evolution, resistance mechanisms and patient stratification. The global significance of circulating nucleic acids lies in their potential to personalise care, reduce invasive procedures and improve outcomes through earlier intervention and adaptive treatment strategies.

Research from Nature Portfolio

Recent studies have demonstrated that postsurgical ctDNA detection in resectable colorectal cancer robustly stratifies recurrence risk and identifies patients most likely to benefit from adjuvant chemotherapy. Longitudinal analysis within a large prospective cohort showed that ctDNA positivity four weeks after surgery was the strongest prognostic factor for relapse and correlated with survival benefit from further treatment. In another landmark study, methylation-based profiling of cfDNA enabled non-invasive detection of multiple common cancers up to four years before conventional diagnosis, achieving high sensitivity and specificity in asymptomatic individuals. A complementary investigation established a comprehensive methylation atlas of human tissues, allowing deconvolution of cfDNA by tissue of origin. This approach validated distinct tissue contributions in healthy individuals and revealed aberrant patterns in sepsis, transplantation and various cancers, thereby providing a framework for future diagnostic assays and mechanistic studies of tumour-derived cfDNA.

Circulating Nucleic Acids in Oncology publication trend

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

Technical terms

Cell-free DNA (cfDNA): DNA fragments circulating freely in the bloodstream, derived from both healthy and tumour cells.

Circulating tumour DNA (ctDNA): The fraction of cfDNA that originates from cancer cells and contains tumour-specific genetic or epigenetic alterations.

Circulating tumour RNA (ctRNA): RNA molecules shed by tumour cells into the blood, which may include messenger RNA and fusion transcripts.

Liquid biopsy: A minimally invasive test that analyses circulating nucleic acids or other tumour-derived components in body fluids.

Next-generation sequencing (NGS): High-throughput DNA sequencing technologies enabling parallel analysis of multiple genomic regions with high sensitivity.

References

1. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nature Medicine (2023).
2. Circulating tumor nucleic acids: biology, release mechanisms, and clinical relevance. Molecular Cancer (2023).
3. Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease. Nature Communications (2018).
4. Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma. Journal of Clinical Oncology (2019).
5. Non-invasive early detection of cancer four years before conventional diagnosis using a blood test. Nature Communications (2020).