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Traditional biopsies can be difficult to obtain but have been the predominant way to diagnose and understand cancer. Liquid biopsies are faster for doctors and easier for patients because they take blood samples rather than tissue samples.

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History and analytes

A biopsy is a sample of cells. In traditional biopsies, this is typically a sample of cells taken from somewhere in the body to be analyzed for cancerous cells. Liquid biopsies involve using blood to screen for cancer before symptoms have manifested themselves and are done in a far less invasive way than many other methods.

Liquid biopsies have been inspired by X-ray, colonoscopy, and Pap smear-based detection techniques. These techniques have led to the discovery and understanding of circulating analytes specific to cancers, such as cell-free tumor DNA (ctDNA), circulating tumor cells (CTCs), and proteins. They can also be used after surgery to indicate the success of tumor removal. For example, studies indicate that patients with CTC in their bloodstream are more likely to relapse.

ctDNA was previously used to monitor patients who had undergone the treatment of advanced cancer. Researchers and practitioners noticed that the levels of ctDNA would increase for months before any visible evidence of a cancer recurrence became obvious.

Because of this, ctDNA is often the analyte of choice for early detection of cancers. In addition to this, ctDNA can be used to check for genetic changes in cancer. This can then in turn be used to inform how a patient will respond to treatment.

In contrast to ctDNA, pediatric amoxicillin dosage chart CTCs are not common in the early stages of cancer. However, they can detect advanced cancers by sensing cancer-specific variants such as androgen splice variants. Out of the available analytes, ctDNA is perhaps the most commonly used.

Difficulties in using liquid biopsies

There are several issues to using liquid biopsies, which appear to arise repeatedly in academic and commercial studies. For one, the levels of analytes, especially ctDNA, circulating the body at any given time are very low. Even tumors of medium size do not produce a high amount of ctDNA. Similarly, CTCs are very rare and occur at levels as low as 1 CTC per 106 – 107 leukocytes.

It can also be more difficult than it can initially seem to extract cell-free tumor DNA. There are often other types of ctDNA circulating in the blood, such as the DNA from the baby’s placenta that can be found in pregnant women. People who have undergone injuries, such as heart attacks or strokes, may also have cell-free DNA in the blood. Because of this, it is important that researchers can correctly identify and distinguish the ctDNA from the other circulating DNA to avoid false positives. This same concept applies to CTCs, which do not have well-defined morphological aspects and can cluster with other cell types.

Lastly, an important problem is identifying the location of cancer, if an analyte is present. The presence of ctDNA can show that there is a tumor, but not where that tumor is. Additionally, since ctDNA can often be detected before the tumor is visible by CT scans, this can be a big hindrance to treatment.

Developments and future directions

Some of the aforementioned issues have been partly solved in recent years. For example, ctDNA can be distinguished from other genetic material using next-generation sequencing techniques. NGS techniques can also distinguish genetic aberrations from epigenetic changes.

Recent developments in this field involve combining liquid biopsy analytes; typically done by cell-free DNA with analysis for known protein markers. Linking liquid biopsies of ctDNA data with other analytes, such as protein markers, can guide the search efforts.

For example, ctDNA detection along with elevated levels of cancer antigen 125 indicates ovarian cancer. So far, protein marker combinations are most accurate for colorectal and ovarian cancers, and leas accurate for liver and lung cancers.

The hope is that liquid biopsies can be used to accurately screen for cancer in clinical practice. Currently, it is not a routine test. To increase its clinical use, some current research efforts are using supervised machine learning to link genetic mutations to particular types of cancer. In addition to showing the presence of cancer, it is hoped that liquid biopsies will be able to indicate the type of treatment that needs to be used if any treatment is required.


  • McDowell, S., 2018. Liquid Biopsy: Past, Present, Future. [online] Available at: <> [Accessed 5 August 2020].
  • Mattox, A., Bettegowda, C., Zhou, S., Papadopoulos, N., Kinzler, K., and Vogelstein, B., 2019. Applications of liquid biopsies for cancer. Science Translational Medicine, 11(507), p. eaay1984.
  • Palmirotta, R., Lovero, D., Cafforio, P., Felici, C., Mannavola, F., Pellè, E., Quaresmini, D., Tucci, M. and Silvestris, F., 2018. Liquid biopsy of cancer: a multimodal diagnostic tool in clinical oncology. Therapeutic Advances in Medical Oncology, 10, p. 175883591879463.

Last Updated: Sep 30, 2020

Written by

Sara Ryding

Sara is a passionate life sciences writer who specializes in zoology and ornithology. She is currently completing a Ph.D. at Deakin University in Australia which focuses on how the beaks of birds change with global warming.

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