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Future of liquid biopsy: Analysis of tumours using biomarkers in blood is beginning to transform cancer diagnosis.

The analysis of tumours using biomarkers in blood is beginning to transform cancer diagnosis, says Catherine Alix-Panabières. The challenge for the future of liquid biopsy now is to make liquid biopsy a standard clinical tool.

During the past decade, liquid biopsy — the analysis of tumours using biomarkers circulating in fluids such as the blood — has received tremendous attention. The ability to detect and characterize tumours in such a minimally invasive and repeatable way could have considerable clinical implications, and huge progress has been made in the development of devices that can do just that. But the technique is not yet a standard tool in the clinical oncologist’s arsenal.

Future of Liquid Biopsy Relies on Utility of These Biomarkers

The abundance of work, involving a wide variety of assays based on different principles, has confused the cancer-research community. In addition, the two most well-developed biomarkers detected by liquid biopsy — circulating tumour cells (CTCs) and circulating cell-free tumour DNA (ctDNA) — are subject to technical variability in the pre-analytical and analytical steps. To address these issues and put liquid biopsy in the hands of more clinicians, the research community must now focus on proving the utility of these biomarkers. Efforts are under way, including the European Liquid Biopsy Society and the US-based BloodPAC project. These consortia, which combine academic and industry expertise, offer hope for the development of robust and reproducible liquid-biopsy assays.

The intention is not to select and refine a single approach to liquid biopsy. In fact, the synergy of multiple circulating biomarkers can reveal the specifics of a cancer. What is important is to identify the specific combinations of markers that signal a cancer’s status, origin and progression, and to make that information available to clinicians. Moreover, it is not only circulating tumour biomarkers that must be considered: as immunotherapy grows in importance as a treatment option, so too does the need to monitor the immune cells of the circulating microenvironment.

Developing an Algorithm to Combine Data Into a Tumour Profile

I therefore urge the development of an algorithm that can combine all these data to obtain a precise tumour profile. Such a development could guide treatment choices. For example, in people with non-metastatic pancreatic cancer, it has been shown that CTCs and extracellular vesicles called exosomes, released by tumours, could be used to diagnose surgically removable tumours1. And a blood test can already detect and localize eight surgically resectable cancers through assessment of levels of circulating proteins and mutations in ctDNA2.

A lack of preclinical and clinical standardization has so far prevented the development of such an algorithm, but progress is being made. For example, the European project PROLIPSY is studying how liquid biopsies can aid the early detection of prostate cancer. The researchers will combine analysis of CTCs, circulating cell-free DNA (cfDNA) and exosomes in people with high serum levels of the protein prostate-specific antigen. The aim is to first identify people with prostate cancer, and then to distinguish those with aggressive cancer from those with non-aggressive disease.

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