Liquid Biopsies: The Next Frontier in Cancer Detection

Authored by: Jixuan (Jason) Zhang

Art by: Amy Em

In the battle against cancer, every advantage matters. Timing is particularly critical, as treatment is more robust and survivability drastically improved when the disease is detected in its earliest stages. Cancer screening is therefore one of the most formidable defenses available. In fact, a study found that between 1975 and 2020, an estimated 4.75 million deaths due to breast, cervical, colorectal, lung, and prostate cancers were avoided due to screening and prevention [1]. However, early detection is easier said than done, and current screening methods have their drawbacks. 

Tissue biopsy, the extraction of cells or tissues for testing, remains the gold standard for cancer screening and is the basis for most established screening tools today. Unfortunately, these tools apply to only a few cancer types (the five mentioned above) [2], and cancers without such established screening account for the majority of cancer deaths [3]. Even for screenable cancers, tissue biopsies often require invasive procedures which carry potential risks for patients [4], only capture information for a localized tumor site, and do not allow for continuous monitoring of disease progression [5]. 

These limitations have motivated research into methods that are not only less risky and invasive but also more broadly applicable. In recent years, liquid biopsy has emerged as a promising alternative to conventional tissue biopsy. Rather than directly sampling tumor sites in an intrusive manner, liquid biopsy analyzes body fluids such as blood, urine, and saliva for molecular biomarkers of cancer such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes [5, 6]. These biomarkers were first observed well before the 20th century [5], but only recently, with the advent of fields like bioinformatics and techniques like high-throughput screening, have they become clinically useful.

Although each cancer releases distinct biomarkers, all of them become conveniently localized to the same body fluids. Liquid biopsies therefore open a comprehensive window into potential tumors throughout the body, something not possible with tissue biopsies. Due to the ubiquitous nature of these cancer biomarkers, liquid biopsies also offer a groundbreaking possibility: the detection of multiple cancers at once, a strategy known as multi-cancer early detection (MCED). 

MCED has quickly moved from proof-of-concept studies to clinical trials. For example, the Galleri blood test assay was recently evaluated in 35,000 individuals aged 50 or older who met the criteria for recommended cancer screening. No serious safety concerns were reported, and Galleri scored, among other metrics, an 88% cancer signal origin accuracy [7], meaning that it predicted the tumor location 88% of the time. A separate MCED test study was able to retrospectively detect cancer biomarkers 3 years prior to the actual clinical diagnosis [3]. 

However, although liquid biopsies/MCED tests show promise, their current implementations are still in their infancy and face several obstacles. First, liquid biopsies are still not sensitive enough to reliably rule out cancers — that is, a negative result does not necessarily indicate the absence of a tumor. Second, liquid biopsies, particularly MCED tests, remain costly and generally uninsured due to their novelty. Finally, and more fundamentally, early detection may not always be beneficial. Specifically, early detection may lead to overdiagnosis — the detection of slow-growing or non-aggressive cancers which act too slowly to cause symptoms or even death — and lead-time bias, when early detection does not alter the time of death [6, 8]. The latter is especially pernicious, as survival (time from diagnosis to death) appears longer simply because diagnosis occurs earlier, not because death is delayed. In addition, early detection may cause more anxiety for the patient. 

Nevertheless, current issues with liquid biopsies/MCED tests are technological hurdles that do not take away from its profound implications. As treatments become increasingly effective, many of these issues will become less and less problematic. Even now, liquid biopsies and MCED tests offer a complementary force to traditional tissue biopsies. Early detection remains a powerful weapon in the fight against cancer, and liquid biopsies/MCED tests may be the innovation that allows us to wield it with unprecedented precision and impact. 

References

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2. American Association for Cancer Research. (2025). Cancer Screening for Early Detection. In Cancer Progress Report. Retrieved from https://cancerprogressreport.aacr.org/progress/cpr25-contents/cpr25-cancer-screening-for-early-detection/ 

3. Wang, Y., Joshu, C. E., Curtis, S. D., Douville, C., Burk, V. A., Ru, M., Popoli, M., Ptak, J., Dobbyn, L., Silliman, N., Coresh, J., Boerwinkle, E., Prizment, A., Bettegowda, C., Kinzler, K. W., Papadopoulos, N., Platz, E. A., & Vogelstein, B. (2025). Detection of Cancers Three Years prior to Diagnosis Using Plasma Cell-Free DNA. Cancer Discovery, 15(9), 1794–1802. https://doi.org/10.1158/2159-8290.CD-25-0375 

4. Crosby, D., Bhatia, S., Brindle, K. M., Coussens, L. M., Dive, C., Emberton, M., Esener, S., Fitzgerald, R. C., Gambhir, S. S., Kuhn, P., Rebbeck, T. R., & Balasubramanian, S. (2022). Early detection of cancer. Science, 375(6586). https://doi.org/10.1126/science.aay9040

5. Ma, L., Guo, H., Zhao, Y., Liu, Z., Wang, C., Bu, J., Sun, T., & Wei, J. (2024). Liquid biopsy in cancer: Current status, challenges and future prospects. Signal Transduction and Targeted Therapy, 9(1), 336. https://doi.org/10.1038/s41392-024-02021-w

6. Wan, J. C. M., Sasieni, P., & Rosenfeld, N. (2025). Promises and pitfalls of multi-cancer early detection using liquid biopsy tests. Nature Reviews Clinical Oncology, 22(8), 566–580. https://doi.org/10.1038/s41571-025-01033-x

7. GRAIL. (2025). GRAIL Announces Positive Top-Line Results From The Galleri® PATHFINDER 2 Registrational Study. Retrieved from https://grail.com/press-releases/grail-announces-positive-top-line-results-from-the-galleriⓡ-pathfinder-2-registrational-study/

8. Croswell, J. M., Ransohoff, D. F., & Kramer, B. S. (2010). Principles of Cancer Screening: Lessons from History and Study Design Issues. Seminars in Oncology, 37(3), 202–215. https://doi.org/10.1053/j.seminoncol.2010.05.006