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Unraveling the Genome

Liquid biopsy for cancer screening, diagnosis, and treatment

Smania, Mary A. DNP, FNP-BC, AGN-BC, FAANP (Assistant Professor)1,2

Section Editor(s): Wysocki, Kenneth PhD, FNP, FAANP; Seibert, Diane PhD, ARNP, FAAN, FAANP

Author Information
Journal of the American Association of Nurse Practitioners: January 2020 - Volume 32 - Issue 1 - p 5-7
doi: 10.1097/JXX.0000000000000359
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Cancer is the second leading cause of death in the United States, with an estimated 1.7 million new cancer diagnoses and more than 606,880 estimated cancer deaths in 2019. As a result, there is a great deal of interest and investment in improving outcomes in this population (National Cancer Institute, 2019). Liquid biopsy (LB) may offer patients and providers a significantly less invasive option for screening, monitoring, and follow-up (De Rubis, Rajeev Krishnan, & Bebawy, 2019). The term “LB” has been coined to define the analysis of a body fluid sample for specific biomarkers in the screening and management of various conditions. Although LB has been used with a several different bodily fluids such as cerebrospinal fluid and urine, blood is most commonly used. Regardless of sample type, LB can provide the genetic characteristic and epigenetic signature of a cancer, allowing oncologists to track the tumors response or resistance to treatment (Batth et al., 2017).

Even before an imaging study is sensitive enough to show a tumor, LB can detect an abnormal genetic signature. Because LB is much less invasive than tissue biopsy, it can virtually eliminate the need for expensive, risky procedures while providing rapid, accurate results (Perakis & Speicher, 2017). In a new cancer diagnosis, LB can be used to guide the selection of an appropriate chemotherapeutic agent based on the tumors genetic profile. Liquid biopsy can also be used to monitor the effectiveness of a selected therapy, detect emerging resistance, and reveal changes in a tumor's genetic signature over time (DeRubis et al., 2019) (Figure 1). Research has continued to expand as researchers work to develop, refine, and establish clinical uses for LB tests. This article provides an overview and guide for nurse practitioners, helping them keep pace with the flood of research and clinical application for this new technology.

Liquid biopsy for screening and diagnosis

Several screening methods are currently used to detect the presence of cancer (Figure 1). Mammography is widely used to detect presymptomatic breast cancer. Mammograms are not perfect and, have limited sensitivity and high false-positive rates which increases the risk of overdiagnosis. Prostate cancer screening is also hampered by the low specificity of prostate-specific antigen (PSA) because PSAs can be elevated for causes other than cancer and resulting in unnecessary procedures, stress, anxiety, and financial burden for patients. Several different types of fecal testing is available to detect colorectal cancers at early stages, including fecal occult blood test, fecal immunochemical test, and fecal deoxynucleic acid (DNA). All these tests suffer from the same problem: low sensitivity and specificity (Sato, Matoba, & Kato, 2019). If an abnormality is found on a screening test, a tissue biopsy is usually necessary to confirm the diagnosis. These biopsies are invasive and have significant limitations, including patient risk, time for pathology analysis, specimen preparation, heterogeneity of the tumor, and procedural costs.

Figure 1
Figure 1:
Uses of liquid biopsy for cancer care.

Liquid biopsies differ from the other screening tests in that cells, and other markers a tumor releases into the bloodstream are collected, offering cancer screening without the risks associated with a tissue biopsy and often before the tumor can be detected by radiologic screening (Wang, Chang, Li, & Sun, 2017). Liquid biopsy offers the opportunity to develop a personalized treatment plan based on the genomic profile of the individual's tumor, whether a breast cancer has acquired the human epidermal growth factor receptor 2 (HER2) mutation, or a lung cancer expresses the epidermal growth factor receptor (EGFR), or whether a particular patient as a colorectal cancer expressing a KRAS (or K-ras or Ki-ras) mutation. Liquid biopsies offer clinicians and patients an opportunity to evaluate serum markers to plan treatment, evaluate response and potential resistance to chemotherapy, and monitor for recurrence or metastasis (Sato et al., 2019).

Components of liquid biopsy

As a primary cancerous tumor develops and grows, various elements are released into the bloodstream. The “tumor circulome” is defined as the subset of circulating components from the cancer tissue that can be collected during an LB. All the tumor-derived elements circulating in the bloodstream can be used, directly or indirectly, as a source of cancer biomarkers, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) (Poulet, Massias, & Taly, 2019).

Circulating tumor cells

Tumor cells are believed to enter the blood stream by either actively pass through a vessel wall or after being passively shed from the primary tumor (Lianidou & Pantel, 2019). These cells are extremely difficult to isolate in the blood, but once retrieved have been widely used to explore the mechanisms and clinical applications of LB. A simple count of freely CTC can be used as a prognostic predictor in many cancers, and the “health” of the circulating cancer cells can be used to monitor the effect of chemotherapy.

Circulating tumor DNA

Fragments of tumor DNA circulating in the blood are more plentiful than CTCs and can be isolated from primary tumors, CTCs, micrometastasis, or overt metastases. The presence of ctDNA after treatment is highly predictive of cancer recurrence and is helpful in monitoring ongoing tumor alterations because of the high turnover rate of circulating DNA and the ability to rapidly assess alterations in the genomics of the tumor mutations, identify epigenetic changes, and look for microsatellite instability (Rossi & Ignatiadis, 2019). The Food and Drug Administration recently approved LB use to assess for EGFR in patients with non–small cell lung cancer, and LB has been used to assess ongoing response to colon cancer treatment including tumor changes and emerging chemotherapy resistance.

Extracellular vesicles, tumor-educated platelets, and circulating tumor ribonucleic acid

Researchers are conducting clinical trials to determine the potential use of other tumor circulome components that have shown promise for cancer screening, diagnosis, and monitoring, including EVs, tumor-educated platelets, and circulating tumor RNA (Ding, Han, Li, & Tan, 2019; Poulet et al., 2019). Both categories of EVs (exosomes and microvesicles) (Ding et al., 2019) are membranous particles that can be found in blood and other body fluids. These nanosized, lipid-coated vesicles communicate information from one cell to another, carrying the molecular fingerprint of the cell of origin. Compared with CTCs, EVs are abundant in circulation and are readily available for collection and study.

Extracellular RNA is a fraction of circulating cell-free RNA arising from cancer cells referred to as ctRNA. Although RNA contains useful quantitative and qualitative information, it is much less stable than DNA, so their use as cancer biomarkers is limited. Tumor-educated platelets that have messenger RNA signatures have recently been shown to be useful in pinpointing tumor location (Poulet et al., 2019).


Tumors shed cells and nucleic acids into the blood stream, and recent advances in precision medicine are providing researchers with the unique opportunity to detect cancer early and monitor treatment efficacy through a simple blood sample. The result obtained from LB is similar to the information retrieved during tissue biopsy, with the distinct advantage of being much less invasive and providing information much more rapidly. Research has continued to expand as scientists and clinicians work to develop, refine, and establish more clinical uses for LB. Liquid biopsy holds some promise in offering clinicians the opportunity to detect cancers before patients have symptoms and as well as more accurately tailor cancer treatment during and after therapy. Advanced practice nurses need to be knowledgeable in genetic testing modalities to select appropriate tests, counsel patients on results, and collaborate with other providers (Table 1) (Greco, Tinley, & Seibert, 2012). Nurse practitioners are perfectly positioned to provide leadership in the translation of genomic innovations in practice, education, research, and policy.

Table 1
Table 1:
Genetic/genomic resources for nurse practitioners


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De Rubis G., Rajeev Krishnan S., Bebawy M. (2019). Liquid biopsies in cancer diagnosis, monitoring, and prognosis. Trends in Pharmacologic Science, 40, 172–186.
Ding D., Han D., Li J., Tan W. (2019). Improving early detection of cancers by profiling extracellular vesicles. Expert Reviews of Proteomics, 16:545–547.
Greco K. E., Tinley S., Seibert D. (2012). Essential Genetic and Genomic Competencies for Nurses with Graduate Degrees. Silver Spring, MD: American Nurses Association and International Society of Nurses in Genetics.
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    Rossi G., Ignatiadis M. (2019). Promises and pitfalls of using liquid biopsy for precision medicine. Cancer Research. doi: 10.1158/0008-5472.Can-18-3402.
    Sato Y., Matoba R., Kato K. (2019). Recent advances in liquid biopsy in precision oncology research. Biological and Pharmacological Bulletin, 42, 337–342.
    Wang J., Chang S., Li G., Sun Y. (2017). Application of liquid biopsy in precision medicine: Opportunities and challenges. Frontiers of Medicine, 11, 522–527.

    DNA; liquid biopsy; precision medicine; tissue biopsy

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