Liquid biopsies are testing techniques that analyze blood samples for cancer cells from a tumor circulating in the blood, or they are used to analyze DNA pieces from tumor cells found in blood. There are three types of liquid biopsy methods, including:

·         Cell-free DNA (cfDNA)

·         Circulating tumor DNA (ctDNA)

·         Circulating endothelial cells (CECs)

It’s worth noting that the potential of using cfDNA was investigated as early as 1947. However, cfDNA was first reported when used in a case that detected cancer in a pregnant woman in 2013. In recent years, liquid biopsy techniques using cfDNA and ctDNA have been useful biomarkers useful in determining a diagnosis and prognosis of solid tumors. However, there are some advantages and disadvantages of using liquid biopsies as new techniques continue to emerge in next-generation sequencing.

What are the Advantages of Liquid Biopsies?

Oftentimes, cancers are present in body organs that are difficult to access like the pancreas, ovaries, or brain. Trying to obtain tissue-resident biomarkers from these types of tumors via surgical biopsy comes with an increased risk of infection or bleeding. cfDNA is released directly into the bloodstream by cellular processes that include apoptosis, phagocytosis, autophagy, and proptosis. DNA levels are higher in patients who have cancer. Structural changes in their DNA sequence are observed, which reflects the process of the disease.

One benefit of liquid biopsies is the real-time information on tumors. This is significant since tumors change over time. Being able to detect these variations in real-time positively impacts treatment modifications which can be more beneficial for patients.

Analyzing DNA from traditional biopsies yields information on which cells are predominant in the tumor. Also, tumor analysis on cfDNA provides information on tumor sites so that the disease and progression can be more accurately monitored. Additionally, cfDNA that the tumor releases into the bloodstream carries the same variants as the tumor cells. This sampling is much easier and allows information to be obtained of various types without inconveniencing patients. Obtaining timely information on different cancer cell variations is a powerful resource when designing modern, targeted therapies.

What are the Limitations of Liquid Biopsies?

Some physicians are not yet willing to rely on liquid biopsies as well as other tests. One of the limitations of the liquid biopsy is the variations cfDNA can present between patients. Cancer patients, in particular, have only 0.1 to 10% of tumor-derived cfDNA. The level of tumor-derived cfDNA can depend on numerous factors, including the cancer stage, tumor burden, tumor vascularization, apoptosis rate, and metastatic potential of the cancer cells. This makes it difficult to detect in its early stages.

The use of tissue biopsy is still the standard for confirming and diagnosing diseases including various types of cancer. They are also useful for determining the disease’s characteristics. Presently, liquid biopsy hasn’t yet replaced tissue biopsy testing, but it is used alongside tissue biopsy.

More clinical trial validation is needed to determine the value of liquid biopsies in medical settings. Additionally, more studies are needed to assess testing accuracy and how effective it is at identifying different tumor types. Presently, it is not known if a liquid biopsy provides a satisfactory sampling of genetic clones in a tumor or if there is some bias specific to the tumor’s sub-regions.

Final Thoughts

The liquid biopsy is emerging as a method to monitor treatment and define targeted therapies. While it is less troublesome for patients, the need for further clinical evaluations exists before it can become the gold standard. The cost factor also comes into play and may impact non-profitable institutions profoundly. Even though it has not yet become the standard in clinical practice, liquid biopsy and its further development are making an impact in clinical research.

References

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/liquid-biopsy

https://www.cancer.gov/news-events/cancer-currents-blog/2017/liquid-biopsy-detects-treats-cancer

https://www.ajmc.com/view/the-promise-of-liquid-biopsies-for-cancer-diagnosis

https://www.cap.org/member-resources/articles/the-liquid-biopsy

https://www.nature.com/articles/d41586-020-00844-5