Liquid biopsy - hot or not? View the full infographic here
Healthcare is chang ing: an ageing population, squeezed budgets, and the emergence of technologies that promise to revolutionise healthcare are combining to create an environment of upheaval. How far these new technologies will deliver on their promises is open to question. What is clear is that the NHS must prepare for innovative technologies, be enabled to try them out and be allowed to accelerate implementation of the best of them.
The PHG Foundation has been investigating the exciting area of molecular diagnostics, focusing on the analysis of circulating tumour DNA (ctDNA) as a 'liquid biopsy' in the management of cancer. ctDNA is released into the patient's blood stream by tumour cells as they die or are broken down. Using a blood sample from the patient, clinicians can extract and then sequence the ctDNA to better understand the genetics of a patient's tumour.
Not only can this technique be used in patients in whom it is not possible to take a solid biopsy (either because they are too ill or the tumour is hard to reach) but multiple blood samples can be taken through time with relatively little effort to monitor disease progression. The information gained from these tests can be used to plan treatment based on the genetic profile of the tumour, monitor response to treatment, determine mutations that might confer resistance to therapy and monitor the emergence of resistance, or monitor relapse.
There are many questions yet to be answered about the biology of ctDNA such as how ctDNA is produced by cancer cells and under what circumstances; and larger scale clinical trials are needed in many areas to determine the utility of the technology on a large scale. Challenges remain, including standardisation of methods, collection of sufficient phase III clinical trial data to demonstrate effectiveness of the technique and the development of reports to give clinicians a clear indication of the actions necessary following a specific test result.
That said, our work shows that many tests could emerge on the market soon. One technology already in use in clinical practice on a small scale aims to determine whether a cancer is eligible for treatment by drugs known as tyrosine kinase inhibitors (TKIs ). Tumours from patients with non-small cell lung cancer are tested for mutations in the EGFR gene - a positive result means the tumour should respond to treatment using TKIs.
This type of test is known as a companion diagnostic and is a good example of a practical use of the technology to stratify patients according to the genetics of their cancer and ensure that patients are not given drugs unnecessarily.
Liquid biopsy testing will make companion diagnostic testing available to the 30% of lung cancer patients in whom solid tumour biopsy is not possible. In addition, the ease of taking a blood sample means that patients' cancers can be monitored for the emergence of mutations that confer resistance to TKIs, indicating that therapy should be switched.
There are plans to extend use of this technology more widely. However, questions surrounding ctDNA companion diagnostics, and tests that focus on specific mutations to aid drug selection, remain:
Increasing patient accessibility to novel technologies
As we have said before (and will doubtless say again) it is vital that the NHS supports its innovators, is prepared to take risks and is able to capitalise on those risks. While ctDNA technologies build on the successes of analysing foetal DNA for non-invasive prenatal testing, and show clear promise for the treatment of cancer, the technology is still new, there are uncertainties about its clinical utility, and financial costs are unclear. Also questions around implementation must be addressed:
Looking beyond lung cancer, there is great interest in developing ctDNA technologies to monitor disease and even to diagnose cancer in asymptomatic patients, challenges which we have discussed previously. It is therefore vital that we learn from the successes and the challenges faced by those who are establishing services now, and use this knowledge to ensure that this technology is developed appropriately and available equitably in the future.
Read more PHG Foundation perspectives on what's hot (or not) in healthcare futures.
Laura provides support for a variety of projects at PHG Foundation, including infectious disease genomics.More about Laura