A new liquid biopsy for cancer could be as much as ten times more sensitive than current methods, according to new research.
Led by the Cancer Research UK Cambridge Institute at the University of Cambridge with Cancer Research UK funding, the findings could pave the way for the development of pinprick home blood tests to monitor patients, developers say.
Researchers used personalised genetic testing of patients’ tumours to look for different genetic mutations in circulating tumour DNA (ctDNA).
This “liquid biopsy” is important for monitoring cancer patients because it can indicate if the treatment was successful or not, or if the patient might relapse. However, the sensitivity of the methods depends on if the individual has a high enough number of mutant pieces of DNA.
When the team combined the testing with new methods to enhance the signal, they reached a level of sensitivity that in some cases could find one mutant DNA molecule amongst one million pieces of DNA, about ten times more sensitive than previous methods.
They say their findings, published in the latest edition of Science Translational Medicine, could lead to tests that more accurately determine if a patient is likely to relapse after having treatment.
Dr Nitzan Rosenfeld, senior group leader at the Cancer Research UK Cambridge Institute, said: “Personalised tests that can detect if cancer is still present, or find it early if it is returning, are now being tested in clinical trials.
“Whilst this may be several years away from clinical use, our research shows what is possible when we push such approaches to an extreme. It demonstrates that the levels of sensitivity we’ve come to accept in recent years in relation to testing for ctDNA can be dramatically improved. At present this is still experimental, but technology is advancing rapidly.”
The new technique looks for hundreds or even thousands of mutations in each blood sample and can often achieve a sensitivity of one mutant molecule per 100,000. In optimal conditions, the method can reach a level measured in parts per million, say the researchers.
The researchers studied samples from 105 cancer patients, testing the method on small sets of patients with five different cancer types, with both early and late stage disease.
The method was able to detect ctDNA at high sensitivity in patients with advanced breast and melanoma cancer, and in patients with glioblastoma, which is notoriously difficult to detect in blood.
The test was also able to detect ctDNA in patients with earlier-stage disease, where the level of ctDNA in the blood is much lower and difficult to find, and included people with lung or breast cancer, as well as those with early-stage melanoma who had already undergone surgery.
The researchers now plan to use the new technique to measure ctDNA levels in individuals who are at high risk of developing cancer to help refine future tests for cancer early detection.
The study is one of several highlighting improvements in detection of cancer biomarkers, reported in the journal last night.
ctDNA monitoring using patient-specific sequencing and integration of variant reads. Science Translational Medicine 17 June 2020
https://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaz8084
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