Liquid biopsy – a revolution in the diagnosis and therapy of cancer?
Liquid biopsy – a revolution in the diagnosis and therapy of cancer ? In order to diagnose and / or rule out a cancer, a tissue sample (biopsy) and a histopathological examination are usually taken. For the analysis of an already diagnosed tumor, a tissue diagnostics with a subsequent molecular pathological examination of the processed tumor cell DNA is carried out. These procedures are intended to provide an optimal therapy in the context of personalized cancer medicine.
In recent years, a new analytical method has caused a sensation: Liquid biopsy (“liquid biopsy“), the blood-based nucleic acid analysis for the detection of tumor cells or tumor DNA in the blood. Because tumor cells also emit genetic information into the blood, which can be examined for gene changes. However, they are only available in small quantities in the blood, which is why they were first made possible by the development of new methods for the highly sensitive detection of nucleic acids such as “digital droplet PCR” (ddPCR) or “next generation sequencing” (NGS).
Sources of tumor DNA in the blood
In the blood, there are two major sources of tumor DNA visible through molecular analysis: circulating tumor cells (CTCs) and cell-free DNA (“cell-free DNA”, cfDNA). The Liquid Biopsy also enables the detection of cell-free mitochondrial tumor RNA (cfmiRNA) and the detection of exosomes. From the point of view of pathology, however, the term liquid biopsy is incorrect because it is a question of pure molecular anaesthetic, not a biopsy in the pathological sense.
The method of liquid biopsy is used in oncology for various purposes, For screening and early detection of cancer, or for assessing the risk of metastasis. An important field of application is also the identification of therapeutic target structures and resistance mechanisms, as well as tumor monitoring.
Help with tumor monitoring and therapy
“Tumor monitoring by means of liquid biopsy is particularly interesting, because it can recognize possibly recurring tumors very early as well as their possibly modified molecular profile can decrypt,” writes the molecular succession Prof. Edgar Dahl (Aachen) in the Deutsches Ärzteblatt. “If, for example, resistance mutations occur under the first-line therapy, the patient’s survival can be significantly improved by a switch (switch) of the targeted therapy (this is the hope).”
Analysis of known driver mutations
The analysis of genes which have already been identified as relevant by the classical tumor screening technique – for example the driving mutations in the genes EGFR, KRAS, NRAS, BRAF or PIK3CA – is relevant for the monitoring and therapeutic purposes. For example, Garcia-Murillas et al. Show that blood-based DNA analysis can help predict a recurring recurrence. In breast cancer patients they had followed the driver mutations identified in the primary tumor and found that an increase in the driver mutation was associated with an early relapse.
An example of the use of the Liquid Biopsy in monitoring is the therapy control in lung cancer patients: researchers linked the findings of the Liquid Biopsy with the clinical data of the patients and were thus able to follow in real-time how the tumors responded to cancer drugs.
Advantages and limitations of the procedure
The advantage of Liquid Biopsy is obvious – instead of invasive sampling, a blood sample is enough. The method is therefore also suitable for types of cancer in which a needle biopsy is risky, Eg in lung or brain tumors.
For the German Society of Pathology (DGP) the use of the Liquid Biopsy is, however, under reservation. Because there is still too much uncertainty in the procedure in order to be able to make reliable statements for diagnostics or therapy. Cell-free circulating tumor DNA is not detectable in all but approximately 70 percent of the metastatic tumor diseases. According to the authors, the authors of the opinion “The chances and risks of blood-based molecular phlogistic analysis of circulating tumor cells (CTC) and cell-free DNA (cfDNA) in personalized cancer therapy“. For brain tumors, the cfDNA detection is even completely unsuitable because of the blood-brain barrier, since only very few DNA fragments could be found in the blood, according to the opinion.
Critically, some molecular pathologists also consider the commercial blood-based analysis of tumor-specific driver mutations. There is still a lack of standardization of existing cfDNA isolation and analysis technologies as well as the quality management of sample processing.