One of the biggest obstacles to surviving cancer is the way the disease can shift its shape and form over time. Tumours are diverse and contain cells of many different types, with different genetic and epigenetic make-up. This allows cancer to adapt to changing environments, survive treatments and spread.
Researchers want to combat this fundamental lethal property to improve treatment. But to study tumour evolution in this way is to chase a fast-moving target. Investigators must track the genetic shifts in cancer cells in real time by setting up prospective assays that sample and analyse tumours during therapy. In theory, it should then be possible to tailor a growing arsenal of cancer drugs to fight emerging patterns of resistance and relapse. But finding a way to do this in the least invasive way represents a formidable challenge — and one that lies beyond the reach of existing tissue biopsies.
There is another way. Over the past few years, interest has grown in developing techniques to analyse cell-free DNA in the blood, such as prenatal genetic testing for fetal DNA in the mother’s bloodstream. As cancer takes hold, the blood fills with free-floating DNA released from dying tumour cells. These genetic fragments could be used to check on the evolution of the tumours they came from. And in a promising clinical study published this week by Nature (C. Abbosh et al. Nature http://dx.doi.org/10.1038/nature22364; 2017), scientists report how they have done just that. What’s more, their trial design — incorporating prospective observations of these circulating fragments of cancer DNA — is a step towards implementing tumour-evolution monitoring as a clinical tool that can dynamically inform treatment.
The clinical data reported online in Nature, and in a parallel paper in the New England Journal of Medicine (M. Jamal-Hanjani et al. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1616288; 2017), describe the results from the first 100 patients enrolled in a trial called TRACERx, which aims to follow the tumour evolution of people with lung cancer who are undergoing therapy. The Nature paper describes a test to assess and compare genetic changes in tumours and in the blood. The dynamic tracking made possible by this “liquid biopsy” sequencing shows that early recurrence of the disease can be detected, and is associated with identifiable features in the circulating tumour DNA.
The results of the analysis support the idea that such liquid biopsies could provide clinical benefit by simplifying procedures and allowing for more-intensive real-time monitoring. Clinical implementation requires additional long-term studies, so that the performance of this type of monitoring can be tested alongside therapy. This is starting to happen: the design of clinical cancer trials is evolving rapidly to accommodate biomarker testing, and a growing number of registered trials are in progress to prospectively monitor tumour progression in the blood.
Still, some challenges remain, including the feasibility and cost of routinely applying liquid-biopsy techniques in clinical practice.
Besides helping to guide clinical decisions, the information derived from close monitoring of tumours with liquid biopsies can be readily fed back to the cancer-research pipeline. Investigators can use this information to work out the mechanism behind the remarkable plasticity of tumours, and translational colleagues could then build on these insights to provide clinicians with improved cancer-killing drugs.
Nature is pleased to bring to our audience this type of clinical study. Such research should not only help convert research findings into medicines, but also provide a wealth of information for basic and clinical scientists. We hope such papers will continue to foster collaboration, and to bridge the gaps between basic and clinical points of view. As they align their sights to parse DNA fragments in the blood, researchers of all types can learn more from patients about how to help them more effectively.
- Journal name:
- Date published: