A liquid biopsy, also known as fluid biopsy or fluid phase biopsy, is the sampling and analysis of non-solid biological tissue, primarily

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

. Like traditional

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...

, this type of technique is mainly used as a diagnostic and monitoring tool for diseases such as

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

, with the added benefit of being largely non-invasive. Liquid biopsies may also be used to validate the efficiency of a cancer treatment drug by taking multiple samples in the span of a few weeks. The technology may also prove beneficial for patients after treatment to monitor

relapse In internal medicine, relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or r ...

. The clinical implementation of liquid biopsies is not yet widespread but is becoming

standard of care In tort law, the standard of care is the only degree of prudence and caution required of an individual who is under a duty of care. The requirements of the standard are closely dependent on circumstances. Whether the standard of care has been b ...

in some areas.

Types

There are several types of liquid biopsy methods; method selection depends on the condition that is being studied. A wide variety of

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

s may be studied to detect or monitor other diseases. For example, isolation of

protoporphyrin IX Protoporphyrin IX is an organic compound, classified as a porphyrin, that plays an important role in living organisms as a precursor to other critical compounds like heme (hemoglobin) and chlorophyll. It is a deeply colored solid that is not sol ...

from blood samples can be used as a diagnostic tool for

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...

. Cancer biomarkers in the blood include

PSA PSA, PsA, Psa, or psa may refer to: Biology and medicine * Posterior spinal artery * Primary systemic amyloidosis, a disease caused by the accumulation of abnormal proteins * Prostate-specific antigen, an enzyme used as a blood tracer for pros ...

(prostate cancer),

CA19-9 Carbohydrate antigen 19-9 (CA19-9), also known as sialyl-LewisA, is a tetrasaccharide which is usually attached to O- glycans on the surface of cells. It is known to play a role in cell-to-cell recognition processes. It is also a tumor marker used ...

(pancreatic cancer) and

CA-125 Mucin-16 (MUC-16) also known as Ovarian cancer-related tumor marker CA125 is a protein that in humans is encoded by the ''MUC16'' gene. MUC-16 is a member of the mucin family glycoproteins. MUC-16 has found application as a tumor marker or bioma ...

(ovarian cancer).

Mechanism

Circulating tumor DNA (ctDNA) refers to DNA released by cancerous cells into the blood stream. Cancer mutations in ctDNA mirror those found in traditional tumor biopsies, which allows them to be used as molecular biomarkers to track the disease. Scientists can purify and then analyze ctDNA using

next-generation sequencing Massive parallel sequencing or massively parallel sequencing is any of several high-throughput approaches to DNA sequencing using the concept of massively parallel processing; it is also called next-generation sequencing (NGS) or second-generation s ...

(NGS) or PCR-based methods such as

digital PCR Digital polymerase chain reaction (digital PCR, DigitalPCR, dPCR, or dePCR) is a biotechnology, biotechnological refinement of conventional polymerase chain reaction methods that can be used to directly quantify and clonally amplify nucleic acids ...

. NGS-based methods provide a comprehensive view of a cancer’s genetic makeup and is especially useful in diagnosis while digital PCR offers a more targeted approach especially well-suited for detecting minimal residual disease and for monitoring treatment response and disease progression. Recent progress in epigenetics has expanded the use of liquid biopsy for the detection of early-stage cancers, including by approaches such as

Cancer Likelihood in Plasma Cancer Likelihood in Plasma (CLiP) refers to a set of ensemble learning methods for integrating various genomic features useful for the noninvasive detection of early cancers from blood plasma. An application of this technique for early detection of ...

(CLiP) . Liquid biopsies can detect changes in tumor burden months or years before conventional imaging tests can, making them suitable for early tumor detection, monitoring, and detection of resistance mutations. The increase in the adoption of NGS in various research fields, advancement in NGS, and increase in the adoption of personalized medicine are expected to drive growth in the global liquid biopsy market.

Clinical application

The CellSearch method for enumeration of

circulating tumor cell A circulating tumor cell (CTC) is a cell that has shed into the vasculature or lymphatics from a primary tumor and is carried around the body in the blood circulation. CTCs can extravasate and become ''seeds'' for the subsequent growth of additional ...

s in metastatic breast, metastatic colon, and metastatic prostate cancer has been validated and approved by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

as a useful prognostic method. Liquid biopsy for analysis of ctDNA for EGFR-mutated

lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...

is approved by the FDA.

References

{{reflist Biopsy Medical procedures Cancer screening

Types

Mechanism

Clinical application

See also

References