Liquid biopsies: A new diagnostic tool, decades-old science

Liquid biopsy
A liquid biopsy uses a sample of body fluid to provide genetic information about their tumor.

When scientists announced in 2003 that they had mapped the human genome, it burst open the door to the discovery of new cancer diagnostics and treatments. This deep understanding of the human genome led to the development of advanced genomic testing, which helps to identify gene mutations that may be driving cancer growth and targeted therapy drugs designed to attack specific mutations. More recently, the mapping the human genome has led to the development of another critical tool in the cancer-fighting toolbox: liquid biopsies, which may be used to detect cancers early and help to personalize a cancer patient’s treatment.

What is a liquid biopsy?

A liquid biopsy uses a sample of a specific bodily fluid, such as blood, urine or spinal fluid, taken from a patient to provide genetic information about their tumor. Liquid biopsies are designed to be less invasive and may be repeated more often than tissue biopsies, which may require either minor or more extensive surgery. Liquid biopsies may also help capture tissue in hard-to-reach areas of the body.

Liquid biopsy plays another important function, during cancer treatment. When used in combination with biopsies, imaging studies—such as X-rays, ultrasounds and MRIs that are commonly used to diagnose cancer—may help monitor a tumor’s response to treatment and help doctors and clinicians target specific areas in the body for treatments such as radiation therapy, while protecting the surrounding areas.

Mapping the human genome

The Human Genome Project, which cost about $2.7 billion in 1991 dollars, involved researchers from around the world in an ambitious effort that lasted more than 12 years. Their mission: to sequence and map the genes of human beings into one collective set of chromosomes, called the human genome.

Considered for years to be biology’s equivalent to “the moon shot,” the Human Genome Project will continue to impact the diagnosis and treatment of cancer for generations to come. By decoding the genome into approximately 3 billion base pairs of DNA, we can “read nature’s complete genetic blueprint for building a human being,” according to the National Human Genome Research Institute.

Informed by this detailed, elaborate human map, oncologists, in many cases, may be better able to customize a patient’s treatment path. Specifically, this wealth of molecular data is used by oncologists to target specific therapies to the personalized patterns of a tumor.

More than 120 years before the start of The Human Genome project, Australian pathologist Thomas Ashworth first detected circulating tumor cells (CTCs) in a patient’s blood. Ashworth saw that the tumor cells looked different than the patient’s blood cells. He observed that tumor cells were being shed into the bloodstream, a process that may lead to metastasis, or the spread of the cancer to other parts of the body.

Almost a century later, in 1966, scientists found high levels of fragments of DNA, or a patient’s unique genetic code, circulating in blood plasma. These fragments, which are called cfDNA, were discovered in cancer patients in 1989. Two years later, researchers learned that they could isolate specific changes to these DNA fragments, and in 2000, the first liquid biopsy product was developed for commercial use.

Research and approvals

Clearly, much has changed since Ashworth’s observation about his patient in 1869. The mapping of the human genome has helped doctors and researchers better identify specific mutations in CTCs. It also led to a surge in research that’s helping to unlock the potential of liquid biopsies.

In 2020, The U.S. Food and Drug Administration (FDA) approved two liquid biopsy products, which means the federal agency has proven the products to be safe and effective. In August 2020, the FDA approved a  biopsy developed by Guardant Health in Redwood City, California that hunts for signs that mutated cancer cell DNA exists in various solid cancers, such as cancers of the breast or prostate. This test also identifies patients who may benefit from treatment with the drug osimertinib (Tagrisso®) for the treatment of non-small cell lung cancer.

In November 2020, the FDA approved a liquid biopsy developed by Foundation Medicine of Cambridge, Massachusetts, as a companion diagnostic device. The test also identifies patients who may benefit from specific treatments for ovarian cancer, non-small cell lung cancer, breast cancer and metastatic castration-resistant prostate cancer.

Oncologists are also using liquid biopsies to gather real-time information about tumors, sometimes continually, in the hopes of learning something that may impact the patient’s treatment plan—like, for example, that the cancer isn’t responding well to a particular treatment.

Liquid biopsy is a useful complement to current methods of detecting cancer—and it may prove even more useful. An October 2020 study published in Clinical Cancer Research, for example, revealed that a urine-based liquid biopsy test outperformed the traditional method of detecting cancer in the urine.

Called UroCAD, this urine-based liquid biopsy is now being evaluated in a clinical trial for surveillance of urothelial carcinoma, the most common form of bladder cancer, according to the American Cancer Society.

Breast cancer also appears to be a promising candidate for liquid biopsy. Monitoring treatment response and predicting disease progression or recurrence are two areas of interest among researchers, who are optimistic about the use of liquid biopsy in breast cancer clinics. This could have a profound impact in the United States, where breast cancer is second only to skin cancer as the most common cancer among women.

Also promising is the use of liquid biopsy for the detection and treatment of lung cancer, the deadliest of all cancers in the U.S. Researchers in a 2019 study published in the Annals of Translational Medicine observed that a simple blood draw could make this tool “easily reproducible, low risk and perhaps with a low overall cost compared to other methods.”

Liquid biopsy is one potential tool in oncologists’ clinical toolkit for detecting, monitoring and personalizing a patient’s treatment plan. Imaging studies such as X-rays and MRI will continue to inform and guide cancer treatment, but liquid biopsy—which is grounded in a pathologist’s discovery more than 150 years ago—is certainly gaining traction.

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