A blood test to diagnose the 8 most common cancers early

This is not the first time that this type of test has been offered by researchers, but the originality of the CancerSEEK test is that it looks for both DNA segments and proteins from 8 cancers in the blood. It would make it possible to diagnose cancers of the ovary, liver, stomach, pancreas, esophagus, colon and rectum, lung or breast at a very early stage. All this in a single blood test such as can be done in any biology laboratory and for a reasonable price.

the liquid biopsy at hand

Research in recent years has shown that fragments of the genetic material, or proteins, of cancer cells can circulate in the blood, long before the cancer itself was clinically apparent. These fragments of DNA or proteins are released by cells when they die, which happens to all cells.
Looking for these fragments of DNA or proteins circulating in the blood is called a “liquid biopsy,” as opposed to a normal biopsy, which involves puncturing or surgically removing a small piece of tumor for analysis.
This approach is particularly interesting from the perspective of treatment because it can occur at a very early stage, when the tumor is only a few millimeters in size. However, the earlier the diagnosis of cancer, the less damage it has done to the surrounding tissues, the greater the chances of recovery and the less burdensome and painful the treatment.
The CancerSEEK test evaluates the levels of eight specific proteins and the presence of 16 mutated gene segments specific to these 8 types of cancers which circulate in the blood and gives a positive result in 70% of cases in a study on more than 1000 cancer patients published in the journal Science.

Very high specificity

Although this test does not detect all possible cancers in adults, it is in fact not a universal test, it would allow the eight most common cancers to be detected at once. These represent more than 60% of cancer deaths in the United States, as in France. In addition, 5 of the cancers covered by this new test are not currently the subject of any organized screening.
In this study, the combination of proteins and genetic abnormalities sought made this test very specific (over 99 percent) for the 8 cancers involved. This very high specificity is essential in medicine because false positive results could be responsible for numerous unnecessary and costly examinations, or even exploratory surgeries to confirm the presence of a wrongly suspected cancer.
The specificity of this test was evaluated on samples taken from 812 people who did not have cancer (healthy controls) and produced only seven false positive results. The results are published online by the journal Science on January 18, 2018.

Sensitivity that varies depending on the cancer

To assess its ability to detect small early-stage cancers, where there are not yet many malignant cells, and not to miss it, which doctors call “sensitivity”, the test was evaluated in 1,005 patients. with stage I to III non-metastatic cancers of the ovary, liver, stomach, pancreas, esophagus, colon and rectum, lung or breast.
The overall sensitivity of the test, i.e. its ability to find cancer in patients, is 70% and varies from a maximum of 98% for ovarian cancer to a minimum of 33% for breast cancer (where there are other screening tests such as mammography).
For the five cancers that are currently not screened (ovarian, liver, stomach, pancreatic and esophageal cancers), sensitivity ranges from 69% to 98%, which constitutes real progress.

A pragmatic approach

The researchers wanted to limit themselves to a small number of mutated genes and cancerous proteins to keep a certain simplicity, simplicity which does not come with a cheap result.
The researchers first explored several hundred genes and 40 protein markers of the cancers concerned, then reducing the number to just 16 gene segments and eight proteins. In the calculations carried out, this is what appears to be the optimal number. Indeed, the researchers were able to notice that by multiplying the analysis of the DNA circulating beyond a certain number, there was rather a degradation of the quality of the results.
As it stands, the test should thus improve the treatment of cancers of the ovary, liver, stomach, pancreas, esophagus, colon and rectum, lung, and to a lesser extent , breast. If it is confirmed, its effectiveness will make it possible to treat these cancers at a very early stage in people at risk, a stage widely accessible to current treatments.
Many of the most promising cancer treatments available today only actually benefit a small minority of people who are ill by curing them. These are major advances, but the too late diagnosis of cancer in many patients means that these treatments neither cure them, nor put them in prolonged remission. It is a loss of luck for them.
If we want to make progress in treating cancers, we need to diagnose them earlier and therefore start looking at screening more pragmatically. Being aware that no test, whatever it is, will detect all cancers. There will be no universal test!

The considerable advance of liquid biopsy

“Using a combination of selected blood biomarkers for the early detection of cancers can potentially change the way we screen for cancer, and it relies on the same logic of using combinations of drugs to treat cancers,” explains Nickolas Papadopoulos, senior author and oncologist at Johns Hopkins University.
“Mutations carried by circulating tumor DNA can be highly specific markers of cancer and, to capitalize on their high specificity, we sought to develop a test based on a small number of biomarkers, but robust, and capable to detect at least one mutation in the vast majority of cancers. It is, indeed, essential to keep the assortment of mutations low in order to minimize false positive results and to keep these screening tests affordable ”.
The researchers point out that this molecular test is only for cancer screening and, therefore, is different from other tests performed on circulating DNA, which rely on the analysis of a large number of genes associated with a given cancer. in order to identify possible therapeutic targets. Targeted treatments directed against a mutation are indeed the most effective current treatments.

Contribution of artificial intelligence

“A novelty of our classification method is that it combines the probability of analyzing different DNA mutations alongside the measurement of the levels of several proteins in order to make a final synthesis”, explains Cristian Tomasetti, associate professor of oncology and biostatistics.
“Another new aspect of our approach is that it uses machine learning from artificial intelligence to allow the test to accurately determine the location of a tumor at a small number of sites in the body in 83% of people. patients ”.
To identify mutations and target proteins for their test, the research team based their research on the United States’ oldest database: data collected over three decades of cancer genetics research and compiled at the Ludwig Center in Johns Hopkins. This is where the first genetic models of cancer were created.

A test close to routine

This test, called CancerSEEK, therefore opens up the possibility of screening for cancers of the ovary, liver, stomach, pancreas, esophagus, colon and rectum, and cancer with a simple blood test. lung or breast, which are the most common.
It can, in principle, be carried out in any city biology laboratory, at the same time as other routine blood tests, prescribed by the general practitioner. It should be marketed for less than $ 500 (400 Euros) according to its promoters, making it an inexpensive and simpler test than mammography in breast cancer or stool blood testing for cancer. colorectal.
Early detection offers the possibility of reducing cancer treatments and improving patient outcomes. Ideally, cancers would be caught early enough to be cured with surgery alone, but even early cancers that are not curable with surgery alone, will respond to chemotherapy that we have most often.

More important validation studies of this test are currently underway. We will see if it keeps its promises because it is generally at this stage of the validation that the previous tests have shown their limits.