Detecting cancer sooner – before symptoms – means you can intervene earlier and people are less likely to die. While doctors can screen for breast, colon and lung cancer, most varieties of the disease can only be detected after symptoms appear. And though it is far from the only approach, the beauty of blood is that it is minimally invasive to collect. “A relatively simple blood-based test that can screen for evidence of cancer… might improve or even replace some screening programmes over time,” says Jacqui Shaw, professor of translational cancer genetics at the University of Leicester, who studies ctDNA.
Looking for ctDNA has become a viable proposition in recent years because of improvements in DNA sequencing technologies that make it possible to scan fragments and find those few with alterations that may indicate cancer. While other blood-based biomarkers are being investigated, the advantage of ctDNA is that, because it has a direct link to the tumour, it can be very specific at identifying cancer. For that reason, ctDNA is also showing promise as a way to profile and monitor advanced stage cancers, a “liquid biopsy”.
Early detection is a harder problem. Early on, when the tumour is small, there is not as much ctDNA to detect. The women Illumina identified as having cancer were all late, not early stage.
Cancer essentially begins when a normal cell’s DNA gets mutated or altered. From that point, the cell multiplies too often and a mass or tumour of abnormal cells forms. A proportion of the cells invariably die and “shed” genetic material into the bloodstream, mixing with larger amounts of DNA fragments coming from the death of normal cells.
It was first reported that fragments of DNA carrying cancer-causing mutations could be found floating freely in the blood of cancer patients in the mid-1990s. The findings caught the attention of Dennis Lo, now a professor of medicine and chemical pathology at the Chinese University of Hong Kong, who thought that “a baby living in a mother is a little bit like a cancer growing in a patient”. Based on that insight, he went on to discover foetal DNA fragments in maternal blood and to pioneer non-invasive prenatal testing (NIPT) (he licensed his patents to Illumina and other companies). He also began, along with others, to apply those insights to how ctDNA fragments might be used in the monitoring and detection of cancer. In 2017, Grail merged with Lo’s company, Cirina, also aimed at early detection.
Results have been published or presented for all these methods, demonstrating that cancer-related signals can be seen. They are based on small studies of 1,000 people or fewer with cancer at various stages. The key for the tests is achieving both a high likelihood of detection (a good sensitivity) and a low false positive rate to avoid needless anxiety and unnecessary follow-up. (In a test being designed for a general population, where cancer actually isn’t very prevalent, the latter is particularly important because even low false positive rates will result in a substantial number of incorrect diagnoses.)