Traditional tissue biopsy typically uses a needle to penetrate the tumour to extract a small piece of sample for the analysis of cancer biomarkers. Despite its necessity to verify cancer diagnosis, tissue biopsy is a minor surgery with multiple drawbacks:
Liquid biopsy circumvents most, if not all, limitations of tissue biopsy (Table 1). As liquid biopsy is akin to routine blood testing, it is non-invasive, less painful, cheaper, more time-saving and more practical for longitudinal monitoring compared to tissue biopsy. About the more complicated aspects, liquid biopsy also captures tumour heterogeneity more accurately and poses fewer risks of cancer cell dissemination, infection, and bleeding than tissue biopsy; let us see why.
Tissue biopsy only analyses a tiny portion of the tumour, which may not fully reflect the tumour’s cancerous nature. Most tumours are highly diverse, where cancer cells within the same tumour exhibit different behaviours in gene expression, metabolism, and metastatic capacity. As a result, region selection bias often happens with tissue biopsy, which may underestimate the cancerous capacity of tumours. This may lead to poor choice of treatments and contribute to the prevailing problem of treatment resistance and cancer recurrence in oncology.
In contrast, samples collected via serial liquid biopsy better represent the overall cancer cells from the tumour, thus reflecting tumour heterogeneity more accurately. Liquid biopsy also examines multiple tumours concurrently, given that cancer markers from all tumour sites are released into the blood. The term tumour circulome was coined to reflect the fact that cancer-derived markers (e.g., CTCs, circulating tumour DNA, and tumour-derived proteins and extracellular vesicles) are leaked into the blood, which liquid biopsy can capture (Figure 2).