A new tool to diagnose: liquid biopsies

Liquid biopsies are an example of integrating next-generation sequencing to diagnose and study tumours using only blood or other fluid samples rather than solid tissue. These biopsies are significant in modern medicine, particularly in treating cancer, as they enable the earlier detection of cancers in a less invasive manner. In this article, I aim to explore liquid biopsies, their role in disease detection and issues which arise from their usage.

A liquid biopsy is a test which detects cancerous tumours from the pieces of tumour that break off and circulate in the bloodstream.  A liquid biopsy involves a simple blood test and analysis in the lab with a machine that separates blood cells from the plasma, allowing a pathologist to examine the fluid and look for biomarkers. These include circulating tumour cells (CTC) or circulating tumour DNA (ctDNA). CTCs are cancer cells that disseminate from a tumour and travelling in the bloodstream, whereas ctDNA is a DNA fragment from the tumour circulating in the blood. See Figure 1 for a diagram summarising this process in more detail.

Finding these biomarkers shows evidence of a malignant tumour, possibly revealing its stage of development and potential metastases. Oncologists use this information to form the basis of cancer prognosis. Furthermore, genetic data from these tests provides information on suitable and effective treatments specific to the patient. In particular, the suitability for targeted therapies, which target specific genes or proteins within the cancer. Furthermore, it can monitor how well a treatment is working by seeing if the tumour has stopped growing after treatment. Finally, it can be used to predict and help prevent recurrence of cancer or progression of cancer by detecting minimal residual disease (where a small number of cancer cells remain in the body after treatment).

Liquid biopsies are perhaps better and more advantageous than normal biopsies, as the method is quicker without requiring surgical intervention. In addition, liquid biopsies provide a more comprehensive tissue profile by taking tumour heterogeneity into account.

This includes revealing more information about genetic variations, monitoring clonal evolution, assessing treatment resistance, and aiding in the customisation of targeted therapies. This means a more comprehensive view is provided compared to tissue biopsies, which do not represent the entire genetic diversity of a tumour. Liquid biopsies excel in overcoming these limitations by providing a systematic and dynamic assessment of the entire tumour’s genetic diversity. Unlike tissue biopsies, which may miss subclones, liquid biopsies offer a more comprehensive understanding of the overall tumour, making them a valuable tool for precision oncology.  The process is also minimally invasive and only causes minimal pain. While liquid biopsies offer a less invasive means of monitoring diseases, their sensitivity and specificity in detecting biomarkers, such as circulating tumour DNA (ctDNA) or circulating tumour cells (CTCs), might vary, leading to potential false positives or negatives. Additionally, the quantity and quality of biomarkers present in bodily fluids can fluctuate, impacting the reliability of liquid biopsy results for consistent monitoring. Furthermore, the associated cost of analysing liquid biopsy samples and the technology required for accurate detection can pose financial constraints for widespread implementation in healthcare systems. See Figure 2 which summarises the advantages and disadvantages of each method.

Currently, there are a few liquid biopsy tests approved by the FDA to detect cancer within a patient. One example is the “Guardant 360 CDx”, approved for use in people with non-small cell lung cancer (NSCLC). Another example is the “Foundation One liquid CDx”, which is approved for use in people with a range of cancers such as NSCLC, prostate, ovarian and breast cancer. However, more research is needed to clinically evaluate the efficacy of liquid biopsies when compared to tissue biopsies. Nevertheless, liquid biopsies show a positive prospect for cancer diagnosis. Furthermore, liquid biopsies have also been used outside of cancer, such as in cardiovascular conditions such as myocardial infarction. In myocardial infarction, specific miRNA signatures released during myocardial necrosis provide accurate early detection of myocardial infarction. Further highlighting the multilevel potential of liquid biopsies.

One of the main ethical concerns surrounding liquid biopsies involves the revealing of sensitive genetic information about a patient, encompassing medical history, and genetic identity, and potentially impacting familial relationships and legal affairs. This raises critical issues regarding privacy, consent, and the secure storage of such sensitive data. Additionally, challenges surrounding standardisation, cost-effectiveness, and the establishment of robust regulatory frameworks for the handling and storage of this genetic information further underscore the ethical complexities and necessity for stringent protocols in the implementation and management of liquid biopsy technologies.

To conclude, it is clear that liquid biopsies have a lot of potential in diagnosing patients and, therefore, treating patients by aiding clinical decisions made by healthcare professionals. It has proven to be useful not just in diagnosing cancer but also in cardiovascular conditions such as myocardial infarction. The process has the potential to improve future patient outcomes. However, for this to happen, issues such as costs and ethics must be addressed so that liquid biopsies can be utilised more effectively in clinical practice. 

Written by Harene Elayathamby

References: 

1. professional, C.C. medical  Liquid biopsy: What it is & procedure details, Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/diagnostics/23992-liquid-biopsy (Accessed: 19 December 2023). 

2. A tale of two biopsies: Liquid biopsy vs tissue biopsy (no date) Biochain Institute Inc. Available at: https://www.biochain.com/blog/a-tale-of-two-biopsies-liquid-biopsy-vs-tissue-biopsy/ (Accessed: 19 December 2023). 

3. Adhit, K.K. et al. (2023) ‘Liquid biopsy: An evolving paradigm for non-invasive disease diagnosis and monitoring in medicine’, Cureus [Preprint]. doi:10.7759/cureus.50176. 

4. Mannelli, C. (2019) ‘Tissue vs liquid biopsies for cancer detection: Ethical issues’, Journal of Bioethical Inquiry, 16(4), pp. 551–557. doi:10.1007/s11673-019-09944-y. 

Figures: 

1.  Journey of a liquid biopsy (no date) Diagnostics. Available at: https://diagnostics.roche.com/global/en/article-listing/infographic-journey-of-a-liquid-biopsy.html (Accessed: 19 December 2023). 

2. A tale of two biopsies: Liquid biopsy vs tissue biopsy (no date) Biochain Institute Inc. Available at: https://www.biochain.com/blog/a-tale-of-two-biopsies-liquid-biopsy-vs-tissue-biopsy/ (Accessed: 19 December 2023