In recent years, new molecular tests have been showing up on my radar. Some of these tests make fantastic claims, such as a simple blood test able to screen for a multitude of cancers before you even have symptoms. I have also seen reports from a saliva test that says it can tell you if you are at risk of having oral cancer in the future. These tests tout the ability to detect the possibility of cancer in patients without them having to undergo traditional “invasive” screening tests such as colonoscopies and mammograms. The possibility of testing for cancer with a simple blood test was intriguing to me, so I decided to find out more about these molecular tests.
Most of these tests look for either circulating cell-free DNA fragments (cfDNA) or circulating tumor DNA fragments (ctDNA). cfDNA are extracellular fragments of double-stranded DNA (dsDNA) between 120-220 base pairs long, which are released from cells undergoing apoptosis. The levels of cfDNA can be increased by physical exercise and in certain pathological processes such as inflammation, sepsis and myocardial infarction. When tumor cells undergo apoptosis or necrosis, they produce a special kind of cfDNA called ctDNA, which is shorter and more fragmented. Another element targeted by these tests is exosomes. These are spherical lipid bilayer vesicles, 40–160 nm in diameter, which are produced by cells in both physiological and pathological conditions. In these tests, exosomes are isolated through ultracentrifugation and then are examined for molecular contents. Once cfDNA, ctDNA, or exosomes are identified, molecular studies are performed looking for mutations specific to certain cancers.
Johns Hopkins is currently in the process of performing clinical trials on their CancerSEEK test which evaluates levels of eight common cancer proteins and can detect the presence of sixteen cancer gene mutations from DNA circulating in the blood. The eight cancers that the CancerSEEK test looks for are cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung and breast. The initial results of the clinical trials have been very promising, with an overall specificity rate of 99% and a sensitivity rate among all eight cancers of 70%.
On the other end of the spectrum, there are some tests which claim to test for “all cancers”, despite only looking for 1-2 proteins or genetic mutations. Some of these tests may also be measuring levels of ctDNA and exosomes and extrapolating a cancer diagnosis from that information. I have to wonder: if a patient goes to their primary care doctor and receives a “positive” result from this second kind of test, what will they do with the information? Likely, they will need to undergo more screening tests, including imaging and perhaps biopsy to ultimately determine whether or not they have cancer.
For me, the ability to test for only a limited number of cancers seems more reasonable. The CancerSEEK test looks for the most common mutations in the most common cancers. The researchers are also careful to point out that not every type of cancer will be picked up as many tumors have different mutations than the most common ones. The technology within these multicancer early detection tests is certainly interesting and exciting. However, long-term studies regarding cancer mortality will be necessary before this type of testing becomes more widespread. In terms of currently available testing, laboratorians and consumers must understand the actual targets and the limitations of testing. The currently available tests can be expensive (~$1,000 and up) and may not be covered by insurance. The cost of a false positive must also be taken into account, and the emotional toll on the patient will be great. Overall, I am excited to learn more about this new testing and eager to learn more about long-term studies that are taking place at cancer centers around the country. For now, I still plan on getting my mammograms, colonoscopies and Pap smears done at the prescribed intervals.