Liquid biopsies: testing times ahead for neuroblastoma

Imagine a future where simple blood tests provide an efficient, painless and non-invasive way to track changes in cancer patients and guide treatment.

For children with cancer, it’s their parents who have to make difficult decisions about invasive tests. Fortunately, we’re on our way to a future of simpler testing for one of childhood’s more common cancers — neuroblastoma — as we heard at a recent international research conference in Cairns.

Neuroblastoma is a childhood cancer of specialised nerve cells which are involved in the development of the nervous system and other tissues. Neuroblastoma can occur in the chest, neck and near the spine; however, it most commonly occurs in the adrenal glands, which are located on top of the kidneys. The average age of diagnosis is just two years old.

Neuroblastoma claims more lives of children under the age of five than any other cancer. Over 20 babies and toddlers will die from this disease in Australia this year and a third of survivors will have long-term side effects from their treatment. The survival rate for the most aggressive form of neuroblastoma is less than 50%.

There is much more to be done in the battle against neuroblastoma. Approximately 400 medical researchers and clinicians from around the globe gathered in Cairns from 19–23 June to share progress. The Advances in Neuroblastoma Research Congress (ANR 2016) was the first ANR congress to run a session specifically on so-called liquid biopsies, reflecting burgeoning international interest in this area of cancer research.

Breaking with tradition

When a patient, adult or child, is diagnosed with cancer, a tumour sample is taken to try to identify as precisely as possible the type of cancer so effective treatment decisions can be made. But a biopsy is generally only taken at diagnosis. Why? Traditional biopsies are invasive. They are often painful and sometimes difficult to obtain.

The problem with one-off biopsies is that tumours change. They are heterogeneous across both space and time. Cancer cells mutate and evolve. As the selective pressure of various treatments is applied to the diverse cancer cell population, some cells survive and continue to accrue mutations. The genetic and molecular makeup of a tumour at diagnosis will not be the same as that of tumours cells obtained following relapse.

Liquid biopsies are emerging as an efficient and non-invasive way to track changes in the cancer of individual patients. Instead of using samples direct from the tumour, testing is performed on circulating tumour cells (CTCs) or circulating DNA (ctDNA) shed by the tumour in the blood or lymph. Collecting samples is quick and easy and relatively painless. Having data from different time points is particularly important in an era of personalised medicine.

The bulk of research on liquid biopsies for neuroblastoma is being conducted in Europe and North America. Several speakers at ANR 2016 made the point that multiple relapses are evidence of branching evolution and tumour heterogeneity (spatial and temporal) with multiple mutations taking place over time. This suggests early, more frequent liquid biopsies could guide treatment and improve survival.

Neuroblastoma researchers aren’t the only ones talking about the potential of liquid biopsies. At a recent US conference, the American Society of Clinical Oncology meeting in Chicago, findings were presented from one of the largest liquid biopsy studies to date. The results from ctDNA tests of 15,000 patients were promising and correlated well with conventional biopsy data.

Progress in Australia

Here in Australia, work is underway on liquid biopsies for both adult and child cancers. Interestingly, the discovery that tumour cells circulate in the blood was made by a doctor in Melbourne almost 150 years ago. In 1869, cancer cells seen in the blood under a microscope were reported in the Australian Medical Journal. Today, molecular analysis and technology offers new possibilities. If sufficient numbers of cancer cells can be collected from the circulatory system, it should be feasible to analyse them in minute detail with new techniques like rapid DNA and RNA sequencing, as well as protein analysis.

For example, work is being done in childhood cancer by the group leader of cancer research at Melbourne’s Murdoch Childrens Research Institute, Associate Professor Paul Ekert. He is starting a spinoff project from the Zero Childhood Cancer personalised medicine program co-led by the Children’s Cancer Institute and Sydney Children’s Hospitals Network. He will explore whether the genetic signature of neuroblastoma can be found in blood to diagnose and track neuroblastoma tumours detected by ultrasound.

In adult cancer, recent news showed the power of circulating DNA blood tests for treating colorectal cancer. Researchers designed a blood-based screening test to determine a patient’s risk of cancer recurrence after surgery. The study involved patients in 13 Australian hospitals and researchers from the Walter and Eliza Hall Institute, Ludwig Institute of Cancer Research and others.

To conclude, research progress in liquid biopsies is very exciting. There are still technical hurdles, but they are being addressed and gradually overcome. Work in this area offers an insight into where personalised medicine for childhood cancer is headed. It may be some years away from being everyday reality in cancer care, but in future we could have routine, regular, non-invasive blood tests for cancer patients to manage their disease and improve survival. At the next ANR conference, in San Francisco in 2018, there will likely be more progress to announce, bringing it all just that bit closer.

*Professor Murray Norris AM is Deputy Director and Program Leader of Molecular Diagnostics at Children’s Cancer Institute. He is also Director of the UNSW Centre for Childhood Cancer Research.