Are liquid biopsies the new benchmark for cancer diagnostics?

Liquid biopsies, a relatively new technology in cancer diagnostics, have shown great potential in their ability to detect cancer early, thereby significantly improving the chances of successful treatment. A liquid biopsy is a non-invasive method for the early detection of a tumour and the monitoring of it during treatment, and which provides data concerning the relapse of a tumour long before any symptoms can be observed. Liquid biopsies analyse bodily fluids (mainly blood) for identifying various biomarkers including proteins such as:

• circulating tumour cells (CTCs);
• circulating tumour DNA (ctDNA);
• cell-free DNA (cfDNA); and
• ribonucleic acid.

The liquid biopsy global market is expected to reach $3 billion by 2022 at a compound annual growth rate of 26%, predominantly due to the increasing number of cancer diagnoses and favourable government initiatives.

CTCs, which are the precursor to metastasis, are often used as the biomarker in liquid biopsies. The Food and Drug Administration (FDA) has also approved CTCs to predict the outcome of a cancer case. Veridex’s CellSearch has been cleared for clinical use in breast, colorectal and prostate cancer patients, but research is focused on using CTCs for various other forms of cancer as well. Alternatively, ctDNA is a relatively new biomarker which has many advantages over CTCs. Tumours continuously shed DNA into the bloodstream by apoptosis; ctDNA is known for tumour mutation and therefore may provide the required information for a suitable course of treatment. ctDNA is preferable to other biomarkers in terms of clinical correlation, as its half-life is approximately two hours and it therefore provides real-time analysis of tumours.

cfDNA has been known about for some time, but its detection and isolation become possible only recently with advancements in sequencing technologies. Since it is in its early stages, cfDNA must overcome many obstacles before it can be commercialised. Most of the patent filings in this domain are focused on isolating ctDNA from the large amount of cfDNA available in plasma, which requires ultrasensitive detection. Patent filings are also focused on detecting suitable markers for the identification of cancer.

It is debatable which available biomarker is most suitable for the diagnosis of cancer. However, a liquid biopsy undeniably offers the following advantages over a standard biopsy:

• Biopsy is a surgical procedure and therefore poses a higher risk to patients in comparison to a blood sample.
• Under-representation of the heterogeneity of a tumour and poor sample availability means that tissue biopsies are of limited value for the assessment of tumours in the advanced stages of cancer.
• Tracking tumour-associated genetic aberrations in the blood can be used to assess the presence of residual disease, recurrence, relapse and resistance.

Key players in the liquid biopsy domain include:

• Roche Diagnostics;
• Qiagen;
• Adaptive Biotechnologies;
• GRAIL;
• Guardant Health;
• Illumina;
• Janssen Diagnostics;
• Myriad Genetics; and
• Trovagene.

So, is liquid biopsy the new benchmark for cancer diagnostics?

Not likely, as the process has a long way to go before doctors can rely solely on the information provided by liquid biopsies. For now, they are used to complement a tissue biopsy and monitor the tumour during treatment.

Before liquid biopsies are adapted as the standard for cancer diagnostics, the following information is required:

• the standardisation of techniques;
• an assessment of reproducibility and cost-effectiveness; and
• an assessment prospective validation in clinical trials.

In future, liquid biopsies may provide diagnostics tests for other diseases, as well as prenatal diagnostics.