In 2012, U.S. DNA sequencing company Illumina was running a new type of blood test on 125,000 expecting mothers to check for genetic abnormalities — such as Down’s Syndrome — in their unborn babies. The tests returned with extremely unexpected results in 10 of the cases. It quickly dawned on researchers that the abnormal DNA they were seeing wasn’t from the unborn, but from undiagnosed cancer in the mothers. Cancers of different types were later confirmed in all 10.
Researchers had not intended this test to be used for cancer screening. However, these results showed that it might be a new purpose for this specific blood test.
In 2016, Illumina created a spin-off company called Grail to place the blood test on the cancer screening market. Grail is on a quest to detect multiple types of cancer in its early stages with the simple blood test that would take under 10 minutes to report results. The test looks at cell-free plasma to find fragments of circulating tumor DNA (ctDNA) sloughed off by cancer cells. Today, the company is backed by more than $1.5 billion in funding with investors to the likes of Bill Gates and Jeff Bezos.
New research on ctDNA points towards it becoming a viable proposition in cancer testing because of improvements in DNA sequencing technologies that make it possible to scan fragments of a tumor with alterations that may indicate cancer. The advantage of ctDNA, as opposed to other blood biomarkers, is that it has a direct link to the tumor and can be very specific at identifying cancer type and aggression. For that reason, ctDNA is also showing a promising way to profile and monitor advanced stage cancers. Researchers are calling it a “liquid biopsy”.
Grail’s ultimate vision, in alignment with the vision of many other competing oncology testing startups, is to someday be able to provide an inexpensive test, ideally no more than $500, that could be administered annually to those over a certain age, with a high chance of detecting different kinds of cancers at once with high accuracy (Grail hasn’t announced a final number but thinks it will be in the region of 10). It’s a test that all of us could one day get.
“The big studies are still to be done,” Nitzan Rosenfeld, a researcher who studies ctDNA at the Cancer Research UK Cambridge Institute and a co-founder of the UK-based liquid biopsy company Inivata told the Guardian, “but there has been considerable progress.”
Detecting cancer in the early stages, before symptoms occur, means a higher chance of survival. Doctors can intervene earlier with treatments and protocols. Breast, colon and lung cancer can all be detected through screening, but most varieties of the disease can only be detected after symptoms appear and the disease has progressed. And though it is far from the only approach, the beauty of blood is that it is minimally invasive to collect.
However, early detection is challenging. When a cancerous tumor is in the early stages, there is not as much ctDNA to detect. The women Illumina diagnosed with cancer in the original finding were all late, not early stage.
Based on a prototype test for detecting epigenetic changes, Grail’s best detection rates ranged from 80% to 47% for nine cancers — ovarian, liver, lymphoma, multiple myeloma, pancreatic, colorectal, oesophageal, head and neck and lung. Breast cancer ranged from 56% to 11% depending on the type. The false positive rate was set at 2%. Further work suggests it could hit less than 1%.
“From a single test, we detected a large fraction of the highest mortality cancers in the early stage with very high specificity,” said Alex Aravanis, Grail’s chief science officer.
Grail’s competitors include Guardant Health, a liquid biopsy company that recently branched out to work on an early-detection test for lung, breast, colorectal and ovarian cancer. There are also multiple academic efforts in the market. Last year, researchers at Johns Hopkins University school of medicine published details of a potential blood test called CancerSEEK that could diagnose eight cancers. And in December last year, University of Queensland researchers created methylscape, a “10 minute test” they say could identify the presence of cancer in the body, but wouldn’t identify where in the body it’s located.
So, when can we expect a once-a-year blood test that checks for multiple cancers? Researchers say it will be at least five years before there is sufficient data to show whether it can work and then it will need to hit the desks of regulators and health economists. Like many other areas of research in the fight against cancer, it is going to take time.