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Liquid Biopsy: Guide, Applications and Techniques
Article

Liquid Biopsy: Guide, Applications and Techniques

Liquid Biopsy: Guide, Applications and Techniques
Article

Liquid Biopsy: Guide, Applications and Techniques

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Liquid biopsies are tests conducted on blood samples that examine biomarkers shed by tumors, such as cancer cells or pieces of tumor DNA. The data from liquid biopsies can be used in place of or alongside that of traditional surgical biopsies. In this article, we review the theory behind liquid biopsies and their applications in cancer medicine.

As it stands today, liquid biopsies are often used alongside surgical biopsies in the diagnosis and treatment of cancer, with each biopsy method delivering unique insights.

How does a liquid biopsy work?

Tumors release a variety of biomolecules into the bloodstream that can be collected via a blood test, separated from the plasma, and studied. The circulating tumor DNA (ctDNA) and intact circulating tumor cells (CTCs) are two of the components that are targeted during a liquid biopsy. The following data are analyzed to obtain insight into the tumor:

  • RNA and protein expression
  • DNA and chromosomal abnormalities
  • Amplification, deletions, and translocations
  • Point mutations

Doctors use this data to learn about a patient’s cancer. A liquid biopsy might be used to determine the best cancer therapy, to track how a patient is responding to treatment, or to discover whether a cancer has returned.

What are the advantages of liquid biopsy over surgical biopsy?

Tissue samples collected from surgical biopsies are considered the gold standard when it comes to cancer diagnosis and treatment because they offer a more in-depth analysis than liquid biopsies. However, there are downsides to tissue biopsies.

Not every tumor is agreeable to a traditional tissue biopsy. For instance, the location or size of a tumor can make tissue sampling difficult or impossible. Even when a surgical biopsy is feasible, the procedure can be invasive and expensive. These downsides limit the frequency with which tissue biopsies can be taken, restricting access to data surrounding cancer progression and treatment response.

Liquid biopsies overcome many of the obstacles that come from surgical biopsies. Because these biopsies are obtained with a simple blood sample, they are non-invasive, allowing for data even when a surgical biopsy is not possible. Additionally, liquid biopsies are often less expensive than surgical biopsies.

Thanks to these benefits, liquid biopsies allow for more frequent testing, which doctors can use to monitor a cancer patient’s disease progression and response to treatments.

Another advantage of liquid biopsies is their potential to detect cancer recurrence before a cancer becomes visible or a patient exhibits clinical symptoms. Following treatment, levels of ctDNA that break off from the tumor and enter the bloodstream drop after the tumor is surgically removed or as the tumor’s size decreases. If the tumor begins to grow back, ctDNA levels increase, and this increase can be detected with a liquid biopsy.

Lastly, the DNA fragments and cancer cells collected from liquid biopsies originate from throughout the body, rather than from a singular tumor site as with a tissue biopsy. As a result, liquid biopsies may pinpoint genetic mutations that would have been missed with a localized surgical biopsy.

Clinical applications of liquid biopsies

The genetic information provided by tumor biomolecules offers insight into the tumor. This information can be used in:

  • Disease prognosis
  • Determining appropriate treatments
  • Measuring a cancer’s response to treatments
  • Looking for cancer relapse post-treatment

Liquid biopsy is a relatively new procedure. As such, present understanding restricts its use to certain forms of cancer, including breast cancer, prostate cancer, colon cancer, and non-small cell lung cancer.

Another, newer application of liquid biopsy is in early cancer detection and evaluating cancer at early stages.

Liquid Biopsy Techniques

The current landscape of liquid biopsy includes two primary techniques:

1.       Circulating Tumor DNA or Cell-Free DNA Tests: Also known as ctDNA tests or cfDNA tests, these tests analyze a DNA from a tumor found in the bloodstream.

2.       Circulating Tumor Cell Tests: Also referred to as CTC tests, these liquid biopsy tests look for whole tumor cells found in the bloodstream. These cells work as metastasis agents that can lead to the growth of additional tumors in sites other than that of the primary tumor.  

Other liquid biopsy techniques are being investigated, including those examining molecules of non-coding RNA and extracellular vesicles known as exosomes.

The Future of Liquid Biopsy

Much of the current research into the potential of liquid biopsy is working to create a simple test to diagnose cancer early. A lot of breakthroughs and improvements are needed to get to this point.

For instance, we need better ways to identify and separate circulating tumor DNA from other DNA fragments found in the blood. From here, researchers must find reliable ways to pinpoint from where, exactly, the tumor DNA originated.

We also need to discover strategies to differentiate between aggressive cancers and those that do not need treatment. Finally, we must learn how to best evaluate treatments based upon the data that we obtain from the liquid biopsy results.

Other potential future targets include the treatment and assessment of cancers that are not currently being targeted with liquid biopsy.

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