Cancer diagnosis can often be an exhausting, extensive process with endless tests, scans, and screenings. We all know the importance of early detection and successful treatments to potentially save thousands of lives every year, so could liquid biopsies offer the lifeline we’ve been holding out for?
Liquid biopsies are an alternative to surgical methods which involve using a blood sample to detect circulating fragments of tumour DNA not associated with a cell, (ctDNA), in the patient’s blood serum or plasma. Conventionally, blood tests are used to detect abnormalities—either in blood cell counts, organ function, or protein and hormone levels. In cancer screening, the presence of certain proteins in the blood is used as an indicator for tumours, e.g. cancer antigen test for detecting ovarian cancer or prostate specific antigen for prostate cancer. These tests have a tendency to suggest many false positives, as a result of many of the indicating proteins being present in other conditions. However, advances in molecular profiling have led to the use of blood samples to study tumour genomics in a much more precise and less invasive way compared to standard methods.
Tissue biopsy, either by surgery or needle, has long remained the established method of tumour diagnosis, but liquid biopsies offer a range of advantages. Because some tumour sites can lie in hard to reach places, tissue biopsies can carry increased risk and difficulty to obtain. The use of liquid biopsies solves this issue, with blood samples being relatively quick and easy to obtain. Both between different tumours and within the same tumour, there is a degree of heterogeneity. For this reason, tissue biopsies may not always be representative of the entire tumour, whereas blood samples can give visibility of tumours as a whole.
Recently, researchers at the John Hopkins Kimmel Cancer Centre in Maryland, US made headlines with news of a single blood test capable of detecting eight different cancers (esophageal, ovarian, hepatic, lung, breast, stomach, and pancreatic) via mutated ctDNA and certain protein presence. Currently, five of these cancers have no screening available—however, sensitivity does vary depending on type. Breast cancer detection was approximately 30% effective, whereas hepatic and ovarian tumours exceeded a 95% detection rate.
The world of medicine is continuously moving towards targeted treatments bespoke to individual genetic profiles and ultimately precision medicine is associated with better outcomes. Using liquid biopsies, the number of RAS mutations detected in metastatic colorectal patients was found to be higher in plasma specimens compared to tumour biopsies for progressing tumours. The ability to consistently obtain samples via liquid biopsy allows for monitoring of tumours and mutations, hence ctDNA has been shown to indicate optimum treatment options and also suggest likelihood of resistance. Similarly, a small study focused on breast cancers, reports the use of liquid biopsies to detect acquired resistance to treatment inhibiting certain proteins known as cyclin dependent kinases.
ctDNA presence in plasma was also used after surgery in melanoma patients to determine prognosis and predict probability of relapse. The majority of patients with detectable levels of ctDNA taken in samples 12 weeks after surgery deteriorated within a year, and so it was concluded that ctDNA may be indicative of relapse in Stage II/III melanoma, where radioactive imaging falls short.
In the last few years, growth of research into liquid biopsies and diagnostics has been exponential
In the last few years, growth of research into liquid biopsies and diagnostics has been exponential, however many studies have been centred around already formed tumours. Evaluation of liquid biopsies as a diagnostic tool is somewhat far away, as researchers have to give enough time for a tumour to develop before recording results. But in terms of tailoring and predicting the right treatment, ctDNA and liquid biopsies appear to offer a much greater insight than tissue biopsies.
Featured image credit: Blood by Mark Marschalko. CC BY 2.0 via Flickr.