In recent years, liquid biopsy technologies have advanced significantly, positioning them as a transformative tool in cancer patient management. While traditional tissue biopsy has long been the gold standard, it is often invasive, painful, and sometimes risky, especially for patients with inaccessible tumours or underlying health concerns. The very mention of “biopsy” can provoke anxiety due to anticipated discomfort and prolonged waiting periods for results.
Liquid biopsy offers a less invasive, faster, and more patient-friendly alternative. Results are typically available within 10 days, and the procedure can be repeated as needed for ongoing monitoring. In situations where tissue biopsy is impractical, such as deep-seated tumours, widespread metastases, or high surgical risk, liquid biopsy serves as a viable and effective option. Moreover, it provides a broader molecular snapshot of the tumour’s genetic landscape, overcoming the spatial limitations of conventional tissue biopsies, which often sample only a small, localised region.
While current liquid biopsy platforms may not yet match tissue biopsy in absolute diagnostic accuracy, ongoing advancements in sensitivity and specificity are rapidly narrowing this gap. As the technology evolves, liquid biopsy is poised to become an integral component of precision oncology. This technique involves the analysis of tumour-derived materials such as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), extracellular vesicles (e.g., exosomes), and tumour-associated microRNAs within bodily fluids, most commonly blood. By enabling real-time molecular profiling of tumours, liquid biopsy is redefining cancer diagnostics, therapeutic decision-making, and disease monitoring, thereby playing a pivotal role in the evolution of precision medicine.
The methodology of liquid biopsy begins with the collection of a peripheral blood sample, typically 5 to 10 mL, in specialised tubes that preserve nucleic acid integrity. Following plasma separation via centrifugation, highly sensitive molecular techniques are employed to detect and quantify cancer-associated genetic alterations. These include point mutations, gene fusions, copy number variations, and epigenetic modifications. Analytical platforms such as quantitative PCR (qPCR), digital PCR (dPCR), and next-generation sequencing (NGS) are central to this workflow. Bioinformatic pipelines further interpret the mutational landscape, enabling clinicians to make informed decisions tailored to the patient’s unique molecular profile.
One of the most significant advantages of liquid biopsy is its capacity for early cancer detection. Traditional imaging and histopathological methods often detect tumours only after they reach a certain size or stage. In contrast, liquid biopsy can identify tumour-specific genetic changes at an earlier, potentially asymptomatic phase, which is critical for improving clinical outcomes. This is particularly valuable in cancers that are typically diagnosed late, such as pancreatic, lung, and ovarian cancers.
Beyond early detection, liquid biopsy offers substantial benefits in guiding therapy selection. By identifying actionable mutations such as EGFR in non-small cell lung cancer (NSCLC), BRAF in melanoma, or PIK3CA in breast cancer, clinicians can select targeted therapies with higher precision. Furthermore, in scenarios where tissue biopsy is unfeasible due to tumour location, patient condition, or insufficient sample quality, liquid biopsy serves as a practical and effective alternative for molecular testing.
Liquid biopsy also plays a central role in disease monitoring and response assessment. Serial sampling enables dynamic evaluation of tumour burden and therapeutic efficacy. The quantification of ctDNA levels during treatment can provide an early indication of response or resistance, often preceding radiographic changes. For example, a rise in ctDNA levels may signal impending relapse or progression, allowing for timely intervention. This approach is also instrumental in the detection of minimal residual disease (MRD), especially following curative-intent surgery or chemotherapy, offering prognostic value and guiding adjuvant treatment decisions.
An additional utility of liquid biopsy lies in detecting resistance mechanisms. Tumours frequently acquire new mutations under therapeutic pressure, leading to drug resistance. For instance, the emergence of the T790M mutation in EGFR-mutated NSCLC confers resistance to first- and second-generation tyrosine kinase inhibitors. Liquid biopsy facilitates the early identification of such alterations, allowing for a rapid shift to alternative therapies, such as third-generation inhibitors like osimertinib.
Moreover, liquid biopsy provides insights into tumour heterogeneity and clonal evolution. Tumours are composed of genetically diverse subpopulations that evolve. Unlike tissue biopsies, which reflect a single spatial and temporal snapshot, liquid biopsy captures a more comprehensive, systemic view of the tumour’s molecular dynamics. This has significant implications for understanding resistance patterns and optimising treatment strategies in real-time.
In summary, liquid biopsy is emerging as an essential tool in modern oncology. Its non-invasive nature, ability for real-time monitoring, and utility in precision therapeutics position it as a powerful adjunct or alternative to tissue-based diagnostics. While ongoing challenges such as assay sensitivity, standardisation, and regulatory validation remain, the integration of liquid biopsy into clinical practice is expected to expand, ultimately enhancing cancer care through more timely, personalised, and effective interventions.