Liquid biopsy: test blood for cancer?

A simple blood test may soon be enough to detect cancer. At the moment, however, the available tests are still lacking in accuracy

Blood Samples: More readily available than tissue samples or ultrasound scans

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The result worried the expectant mother: A new blood test had found two serious genetic disorders in her baby. Just strange that the ultrasound showed a normally developed child. The doctors repeated the test - with the same result. A few months later, the woman gave birth to a healthy boy.

Then the next terrible news: a tumor in her abdomen had already affected several organs. The blood test had not indicated the child's illness - but the cancer of the pregnant woman. Case reports like this made US researchers sit up and take notice. In one study, they looked at data from more than 125,000 expectant mothers. Ten of them were later diagnosed with cancer. And: in all cases, a blood test had previously identified abnormal genetic material.

New ways to diagnose cancer early

The knowledge that malignant tumors can be detected in the blood opens up completely new possibilities for the early detection of cancer. Complex examinations such as mammography screening for breast cancer or colonoscopy, which so many people shy away from, could be a thing of the past. Other types of cancer, for which there is currently no good early detection, could also be detected in the blood - and thus save countless lives. Because if recognized in time, cancer is often curable today.

Professor Klaus Pantel, University Hospital Hamburg-Eppendorf

© W & B / Daniel Butowski

"The potential of the method is huge." Professor Klaus Pantel, Head of the Institute for Tumor Biology at the University Medical Center Hamburg-Eppendorf, is convinced of this. He is one of the pioneers in the field of "liquid biopsy", as experts call the method.

First traces in the blood

In contrast to the conventional biopsy, for which a piece of suspicious tissue is removed and examined, a normal blood sample is sufficient for the new analysis.
It has long been known that cancer leaves traces in the blood - usually some time before diagnostic imaging processes make it visible in the body.

"Isolated cancer cells penetrate the vessel walls early on and travel through the body," explains Pantel. They also secrete small vesicles, so-called exosomes. Specific proteins and bits of genetic material (see graphic below) from dead tumor cells also swim in the blood. Numerous working groups around the world are now looking for the ideal combination of tell-tale signs to safely detect cancer.

Faster and cheaper: New technologies make it possible

"The boom is strongly driven by technology," explains Professor Edgar Dahl from the Institute for Pathology at the RWTH Aachen University Hospital. Modern methods of analysis are able to read the genetic material at high speed and discover even the finest abnormal traces - and increasingly faster and more cheaply.

The advantages of the liquid biopsy are obvious: It is easy to use and can be carried out almost as often as you like. "The blood also provides a kind of overall picture," explains Dahl. When tissue is removed with a biopsy needle, the view is limited to a small area of ​​the tumor.

But such an ulcer is often not of a uniform nature and is constantly changing due to mutations. If the cancer has already spread to other organs, these metastases often have different properties. The liquid biopsy could in principle make all of this visible.

The first tests are already in use, but not for early detection. Because blood does not only tell whether cancer is present. It can also show whether and how this changes during treatment.

Treatment depends on the type of tumor

Before starting therapy, a tumor is usually examined for its special properties. "Medicines can then often be used that block its growth in a very targeted manner," explains pathologist Dahl. However, some tumor cells are or become immune to the drugs. "Cancer becomes resistant to a drug - just like bacteria to antibiotics," said the expert.

Whether this is happening can partly be seen from the genome of the tumor. Therapy can then be changed accordingly. Such a blood test is already used in patients with advanced non-small cell lung cancer.

The liquid biopsy also provides sensational results for a situation that many patients find themselves in: the tumor has been removed and the cancer has been defeated for the time being. But is he coming back? This risk often lasts for many years. Regular follow-up examinations are therefore standard; With the help of imaging procedures, new tumors are searched for.

© W & B / Jörg Neisel

Telltale traces

Long before imaging processes can detect a tumor, it leaves traces in the blood. New analysis methods can not only detect cancer early - they can also show, for example, whether the tumor is spreading.

Blood can evidently reveal this information much earlier. It showed the return of the disease in breast cancer patients - more than six months before images showed new tumors. This is what British researchers report in the journal Science Translational Medicine. "The data are very good," says Pantel. His goal: to start a targeted therapy before the cancer cells multiply again.

There is already a successful model of such treatment: prostate cancer. The so-called PSA test looks for a protein in men that is released by tumor cells in their prostate gland. If the cancerous organ has been removed and the value still rises, treatment is started.

Too often false alarm

The practical hurdles are apparently greater in the area of ​​early detection. There are many approaches. But there is usually a lack of accuracy. "Two values ​​are particularly important for assessing the quality of a test: the specificity and the sensitivity," explains Dahl. The sensitivity states how often the test correctly classifies a sick person as sick. A sensitivity of 90 percent means that the test detects 90 out of 100 tumor patients.

That sounds good. But the value means nothing without specifying the specificity. It describes how often a test classifies a healthy person as healthy and not shows cancer where none is present. "The specificity has to be 95 percent or higher," emphasizes Dahl. If a test comes off badly here, it is unusable, despite perhaps high sensitivity.

That was also one of the problems with the Heidelberg blood test for breast cancer, which was presented to the public in the spring with a lot of media coverage. The alleged sensation turned into a scandal, as the promises made were in no way fulfilled.

Uncertainty due to faulty tests

Dahl warns against the use of such immature tests. If such a large number of healthy people turn into suspected cancer patients, this not only means burdensome follow-up examinations and enormous costs. Above all, it means: fear. "Under no circumstances should too many people be unnecessarily worried," emphasizes Dahl.

Nevertheless, there has been great progress in the area of ​​early cancer detection using blood. For example, last year researchers at the Kimmel Cancer Center in Baltimore (USA) presented a test that detects eight common tumor types - and is extremely rarely wrong in healthy people.

The CancerSeek combines a search for cancer genes with some tell-tale proteins. In a pilot study, the test was able to identify 70 percent of the sick. However, the range ranged from an excellent 98 percent for ovarian cancer to a meager 33 percent for breast cancer.

Not quite suitable for everyday use yet

It is therefore not yet clear whether the test is suitable for an early detection measure for the general public. Experience has shown that the results are worse under everyday conditions. "In the elderly in particular, various pathological processes often take place simultaneously in the body," explains Pantel. This can falsify the result.

But even if the results continue to improve, the new methods also pose new problems for medical professionals. For example, how do you deal with patients in whom tiny tumors are likely to grow - but no one knows where?

However, its use is less problematic for people who already know about their disease - even if, in the opinion of experts, liquid biopsy is not yet an alternative to needle biopsy. "It provides additional knowledge," says Pantel. This can help to choose the optimal therapy or to better assess the risk of the cancer spreading. The more you know about the enemy, the more targeted the attack can be.