Liquid Biopsies: Poised to Revolutionise Cancer Care

Liquid biopsy is a perfect example of how translational research can improve the lives of cancer patients. Caroline Dive, Professor of Pharmacology at Cancer Research UK Manchester Institute, is passionate about the potential of this technology. Here she tells us why she thinks liquid biopsies look set to take the cancer world by storm.

  • Date: 09 Jun 2017

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“Tumour biopsies are still the gold standard for finding out molecular information about a patient’s cancer and if we can get one, we should.” But therein lies the problem. “Obtaining tissue biopsies can be challenging at the best of times and may be impossible in the case of difficult-to-access tumours.” And when repeated tumour samples are required for long-term monitoring, the problem is even greater. “Getting a biopsy over and over again throughout the lifespan of the patient is not practical and, in certain circumstances, not entirely without risk to the patient. For patients with multiple metastases, the situation is further complicated by how many detectable secondary tumours there are and how many of these we can biopsy.”

This, she says, is the beauty of liquid biopsies. “They present us with the opportunity to monitor a whole spectrum of potential tumour biomarkers— circulating nucleic acids, circulating tumour cell (CTCs), circulating proteins—in just 10 mL of the patient’s blood. They can also help to address the problems of heterogeneity, both intra-tumour and inter-site, inherent in tissue biopsies particularly when only a small biopsy is taken.” Progress in this area over the last five years has been incredible. “Everyone is talking about it. Go to any cancer conference and you will see that so many investigators are measuring circulating tumour DNA, what I would call the ‘here and now’ liquid biopsy.”

We can learn a lot about a patient’s tumour from a 10 mL sample of blood.

She remembers exactly how she came to study liquid biopsies. “I joined Cancer Research UK Manchester Institute—then called the Paterson Institute—in 2003 to set up a translational research group focused on biomarkers for personalised medicine. Intending to work with tumour biopsies, I had to change my plans when we were rarely able to obtain tumour samples. Ever the pragmatist I thought, what can I get? I can get blood! Capitalising on my 20 years of research experience, we started looking at circulating markers of tumour cell death, before moving onto angiogenesis biomarkers, CTCs and then circulating nucleic acids.”

The circulating tumour cell patient-derived explant models (CDX) she developed within the Cancer Research UK Lung Cancer Centre of Excellence have transformed research into small-cell lung cancer (SCLC), a notoriously difficult-to-treat disease that inevitably develops chemotherapy resistance. “For the first time ever, we had a model we could use to study the biology of SCLC and, by comparing explants produced from blood samples at presentation and progression, the biology of resistance. We’re now testing new therapies in these models and will be able to translate the information directly to clinical trial designs using CTCs, prevalent in this cancer type, as a readily accessed source of biomarkers.”

One of the biggest questions everyone wants answered is, can liquid biopsies be used for the earlier detection of cancer? “Without doubt, the way to improve outcomes for most cancer patients is by finding their tumours early. To do this, the test has to be both incredibly sensitive and, to avoid false positive results, extremely specific.” It is early detection on which her team is placing future emphasis. ““We’re beginning to build liquid biopsy sample collection into a community-based lung health study that was piloted in Manchester last year, in which mobile computed tomography (CT) scanners set up in supermarket car parks allow access by high-risk and hard-to-reach populations. Through examination of the nucleic acids, tumour cells and proteins in a blood sample taken at the same time as the CT scan, we want to see if we can pick up early signals of disease and, further, determine whether the signals are confined to patients with positive CT scans or if they are also apparent in patients with no CT-detected disease.”

Overall, the potential of liquid biopsies is huge. “They can also be used to give us information on prognostic and predictive biomarkers and to monitor minimal residual disease following surgical tumour removal. In a field in which most patients will eventually stop responding to targeted therapy, the application of liquid biopsies to detect emergent resistance, to find out when it starts and the mechanisms involved, is really attractive.” And she thinks the future benefits of the approach are fairly obvious. “Patients will get the most effective management of their disease, using only a simple blood sample, and clinicians will be provided with a readily understandable blood test result in a shorter turnaround time than that currently achieved for tissue biopsies. Right now, we’re getting results on circulating tumour DNA from patients in our phase I unit in around five working days and we’re confident that in the future turnaround time will only get shorter.” She describes her hopes for this technology. “My dream, which will keep me going until my retirement, is that we reach a point where patients won’t need to go to a hospital to give their blood samples, but will instead be able to do it in their local pharmacy. Samples will be then transported to specialist liquid biopsy laboratories and the results sent directly to the patient’s clinician, the whole process taking only days from start to finish.”

I would like to see blood tests for liquid biopsies become as commonplace as the prick test for diabetes is today.

She thinks the biggest obstacle to the widespread use of liquid biopsies in daily clinical practice is time, time to ensure that the techniques are optimised to produce robust and reliable results. “There will be a period when we will have to evaluate liquid and solid tumour biopsies concurrently. At the end of the day, it will probably be through comparison of these two approaches, alongside imaging, that we will achieve the confidence to say that the liquid biopsy can do the job by itself.”

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This article appeared in the May 2017 edition of ESMO Perspectives.

 

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