Author: Navneet Kaur, McMaster University
New biotechnological inventions and breakthroughs for cancer treatments are being made by doctors and scientists worldwide. One of the most recent and promising advancements is the liquid biopsy, a medical test that detects cancer tumors and holds incredible potential as a non-invasive cancer screening tool. While still being perfected, liquid biopsies have already revolutionized the field of clinical oncology, offering advantages such as easier tumor sampling, continuous monitoring, and screening for therapeutic resistance.1
Figure 1: Various clinical applications of liquid biopsy using CTCs, circulating nucleic acids or other tumour-derived materials in the bloodstream.2
Liquid biopsies have applications in various clinical areas (See Figure 1). Currently, they are used to detect cancerous tumors, such as lung cancer, ovarian cancer, and more.3,4 This technology can be used to diagnose cancer in all stages, and leverages the life cycle of tumor cells for real-time cancer monitoring and detection.5 Throughout a tumor’s life, cancerous cells break off and release their DNA into the bloodstream.6 These DNA fragments are distinct from the DNA released by healthy cells, so a tumor can be detected by extracting and analyzing a simple blood sample for tumor cells and DNA. With proper equipment, a liquid biopsy can also use these blood samples to predict prognosis and describe important information about the cancer, guiding treatment.3,6
A liquid biopsy detects tumors by checking blood samples for the presence of three key indicators. The first is ctDNA, which stands for circulating tumor DNA. ctDNA is a DNA fragment of the tumor controlling its behavior.3 Second is CTCs, circulating tumor cells, which are cancerous cells circulating in the bloodstream. The third and final indicator is biomarkers that signal abnormalities in the body, such as cancer antigen 125 (CA-125).4 With these signatures, a liquid biopsy can confirm the existence of a tumor, pinpoint its location, and provide valuable data to help healthcare providers decide treatment options.
Liquid biopsies are not the only type of cancer detection test, so it is crucial to note the distinction between a liquid biopsy test and its predecessor, tissue biopsy (See Figure 2). Liquid biopsies offer a non-invasive way to detect and diagnose cancer tumors. It can be used multiple times and provides a more comprehensive and robust picture of the cancer type than traditional tissue biopsies.4 If a patient is not well enough for a tissue biopsy, is uncomfortable with the method, or cannot undergo the testing without damaging surrounding organs, then liquid biopsies provide a successful alternative.3 Liquid biopsies can be performed quickly with immediate results to provide continuous real-time monitoring, whereas tissue biopsies may take a few days to show results.
Liquid biopsies are generally more useful than tissue biopsies. However, in cancer detection and confirmation, tissue biopsies remain superior. Liquid biopsy tests search for indicators of a tumor within a small blood sample. However, blood is continuously circulating within the body. As blood circulates, so do the tumor cell fragments and other signs of a tumor in the bloodstream. Due to this constant circulation, tumor cells and antigens can miss getting caught in the blood sample. As such, even if a patient has a tumor, a liquid biopsy test may fail to detect it.3 Tissue biopsies, however, rarely provide results with error. During a tissue biopsy, a doctor will remove tissue samples directly from the suspected tumor source and test them in a lab.3 Due to this direct, surefire approach, tissue biopsies are still the reliable gold standard in cancer diagnoses.4
Figure 2: Comparison of traditional tissue biopsy and liquid biopsy. The schematic illustrates the advantages that liquid biopsies have gained over traditional invasive surgical methods over the past decade. Shown here are methods of extracting a test sample which usually includes a small tissue fragment in case of tissue biopsies and blood in LBs.1
Liquid biopsies hold much promise in non-invasive cancer screening. Due to their greater affordability and accessibility compared to tissue biopsies, they are predicted to become used more frequently in upcoming years to provide equitable access to cancer screening worldwide.6 However, research to improve and explore additional uses of liquid biopsies is still ongoing. The uses of liquid biopsies are currently being globally analyzed, and some promising results are sure to lead to yet another breakthrough in biotechnology and public health.7
Works Cited:
1. Lone S. N, Nisar S, Masoodi T, Singh M, Rizwan A, Hashem S, et al. Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments. Mol Cancer [Internet]. 2023;(21):1–2. Available from: https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01543-7
2. Ignatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic — implementation issues and future challenges. Nature Rev [Internet]. 2020;18:298. Available from: https://www-nature-com.libaccess.lib.mcmaster.ca/articles/s41571-020-00457-x.pdf
3. Professional CCM. Liquid Biopsy [Internet]. Cleveland Clinic. 2024 [cited 2024 Dec 10]. Available from: https://my.clevelandclinic.org/health/diagnostics/23992-liquid-biopsy
4. Adhit KK, Wanjari A, Menon S, Siddhaarth K. Liquid biopsy: an evolving paradigm for non-invasive disease diagnosis and monitoring in medicine. Cureus [Internet]. 2023 Dec 8;15(12). Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10772356/#:~:text=Liquid%20biopsy%20analyzes%20tumor%20DNA,when%20compared%20with%20tissue%20biopsy
5. Chen M, Zhao H. Next-generation sequencing in liquid biopsy: cancer screening and early detection. Human Genomics [Internet]. 2019 Aug 1;13(1). Available from: https://doi.org/10.1186/s40246-019-0220-8
6. Basharat S, Smith A, Darvesh N, Rader T. 2023 Watch list: top 10 precision medicine technologies and issues. Can Journal Health Tech [Internet]. 2024;3(3). Available from: https://www.cda-amc.ca/liquid-biopsy-informing-cancer-treatments
7. Wang H, Zhang Y, Zhang H, Cao H, Mao J, Chen X, et al. Liquid biopsy for human cancer: cancer screening, monitoring, and treatment. MedComm [Internet]. 2024 May 28;5(6). Available from: https://doi.org/10.1002/mco2.564
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