Liquid biopsy (synonym: liquid biopsy) is a blood-based nucleic acid analysis for the detection of tumor cells or tumor DNA in blood.
Sources of tumor DNA are circulating tumor cells (CTCs) and cell-free DNA (cfDNA). Furthermore, the method allows the detection (“tracking”) of cell-free mitochondrial tumor RNA (cfmiRNA) and the detection of exosomes.
However, the term liquid biopsy is inaccurate, as it is a purely molecular analytical procedure. A biopsy (tissue removal) in the sense of pathology is not present, but the material examined is, for example, circulating DNA released from the tumor into the serum (aqueous component of the blood).
Liquid biopsy can detect multiple concurrent resistances.
Indications (areas of application)
- Screening or early detection of cancer
- Estimation of a risk of metastasis
- Identification of therapeutic cell structures
- Analysis of driver mutations in genes (e.g., EGFR, KRAS, NRAS, BRAF, or PIK3C).
- Detection of resistance mechanisms
- Tumor monitoring
The following are publications on the use of liquid biopsy in colon carcinoma (colorectal cancer):
- Screening for mutations (changes in hereditary pattern) in RAS genes in metastatic colorectal cancer to predict response to EGFR monoclonal antibodies; is certainly becoming the ninth gold standard: with the help of DNA analysis, significantly more mutations were detected than by tissue biopsy; another advantage is the speed of evaluation (only 2 days).
- Evidence of recurrence risk (risk of tumor recurrence) after surgical resection (surgical removal) in stage II patients or indication for chemotherapy. Further results are to be awaited.
So far, it appears that tumor biopsy will retain a key position. For example, cell-free circulating tumor DNA is not detectable in all but only about 70% of metastatic tumors (tumor disease associated with the formation of daughter tumors).
In a prospective cohort of 42 patients with molecularly defined gastrointestinal (GI) cancers and acquired resistance to targeted therapy, direct comparison of post-progression cfDNA with tumor biopsy (tissue removal from the tumor) revealed that cfDNA more frequently identified clinically relevant resistance changes and multiple resistance mechanisms. However, relevant genetic alterations for resistance change found by tumor biopsy and not by liquid biopsy were detected in 78% of cases.
As to the current status, it can be said that there are large differences between different tumor types and depending on the tumor stage.
The fact that the Liquid Biopsy saves invasive diagnostics (diagnostic procedure requiring an intervention in the body of the examined person) if necessary, shows a significant advantage compared to tumor biopsy. However, cfDNA detection in brain tumors, for example, is not possible because of the blood–brain barrier, with current methods finding extremely few DNA fragments in the blood.
