Liquid biopsy for precision oncology

Liquid biopsy is a non-invasive way for monitoring a cancer disease, or evaluating treatment response. CBmed has a focus on liquid biopsies, thereby implementing CEN/ISO standards, developing assays and following a multi-analyte approach.

Liquid biopsy essentially stands for the blood-based analysis of circulating tumor cells (CTCs) or circulating tumor derived nucleic acids. For instance, if a tumor is growing, it can shed tumor cells into blood, which are then called CTC. The tumor can also shed circulating tumor DNA into blood, which is then called ctDNA. Both entities are commonly summarized as liquid biopsy, since they contain the same information as a tumor tissue itself. Like traditional biopsy, this type of technique has the potential to be used as a diagnostic- and monitoring tool for diseases such as cancer. So far, the gold standard is a tissue biopsy, where a part of the tumor is retrieved by a needle biopsy in order to analyse it further under the microscope or by molecular diagnostic approaches. With liquid biopsies, a blood sample is taken to isolate CTCs or ctDNA, which allows to reconstruct the genome of the tumor, amongst other parameters.

Advantages and challenges

Liquid biopsies offer manifold advantages: It’s a minimal invasive approach, tumor relevant information can be isolated by simply taking a standard blood sample. Therefore, it can be performed more frequently, opening up new ways to track tumor evolution and changes in the mutational landscape over the course of cancer treatment. In comparison, a tissue biopsy and can not be performed multiple times due to its invasive nature. By taking multiple liquid biopsy samples in the span of weeks or months, it is possible to assess the efficiency of a cancer therapy, and may also inform about the risk of disease relapse. Currently, the clinical implementation of liquid biopsies is limited, primarily due to technical and logistical challenges. Nevertheless, several liquid biopsies assays have been approved by regulators such as the Food and Drug Administration in the US (FDA). Liquid biopsies in lung cancer, for example, are becoming a routine tool for early detection of therapy resistance.

However, on the route for a standardised clinical application, there are still challenges ahead. One of the major drawbacks of liquid biopsies is the low abundance of tumor derived components in blood, especially in localized disease. For example, CTCs are usually only detectable in patients with advanced disease. When a tumor mass is below a certain size, the tumor is difficult to detect by liquid biopsies or imaging approaches. It is one of the major tasks for researchers to improve liquid biopsy assays to allow robust detection of cancer in early stages, where often surgery can be performed with curative intent. A multitude of liquid biopsy technologies have been developed already, they can be separated between cell-based and nucleic acid-based approaches. The many different available technologies create another challenge for liquid biopsy: standardisation of blood samples collection, stabilisation and analysis procedures.

Lab workers at CBmed working with Liquid Biopsy

Liquid biopsy as personalized medicine

CBmed has a strong liquid biopsy focus and is particularly aiming to solve one of the major hurdles: overcoming the quality issue. For example, there is not much data gathered from the time point a blood sample is drawn until it appears at a lab for analyses. This is a black box for the quality of a sample and large consortia developed standards for the collection of blood samples and how they should be processed. For instance, the SPIDIA4P or the CANCER-ID consortium defined ISO and CEN standards that are implemented by CBmed in order to get the best quality of the blood samples.
Besides, CBmed is developing a multi-analyte approach, i.e. analysis of CTCs and ctDNA are complementing each other. This has been exemplified in our recent paper „A multi-analyte approach for improved sensitivity of liquid biopsies in prostate cancer“ (Hofmann et al. Cancer 2020). Data show that three liquid biopsy assays – circulating tumor cells, circulating tumor RNA, and circulating tumor DNA – complement each other. Their combination in a multi-analyte approach drastically improved the diagnostic sensitivity and enabled the identification of resistant patients that would have been missed by the single assays. Ultimately, increased sensitivity of multi-analyte liquid biopsy approaches might enable more precise treatment decisions and bring the benefits of personalized medicine to more patients.

For Liquid Biopsy, CBmed uses most advanced technology.

CBmed is following a multi-analyte approach, i.e. analysis of CTCs and ctDNA are complementing each other.

Partnerships and future projects

For the Liquid Biopsy project, CBmed is working together with several partners. When it comes to clinical partners, the cooperation with the Medical University of Graz and the Medical University of Vienna is well established. Besides, there are several industry partners involved, such as QIAGEN, ViennaLab Diagnostics, GILUPI and CytoGen which are all interested in developing highly standardised workflows to analyse liquid biopsies.
In a clinical setting, liquid biopsies have high potential becoming an additional tool in the diagnostic workflow to treat patients in a precision medicine approach. CBmed is including liquid biopsies in all future cancer projects as it can add valuable information for research and patient care.

The Author

Priv.-Doz. Amin El-Heliebi, Ph.D.
CBmed GmbH, Scientific Area Leader “Cancer”