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Cancer diagnosis from the blood – Fact or fiction?

No. 04 | 27/01/2017 | by Koh

Can a simple blood sample test replace an invasive biopsy of tumor tissue? Can a few milliliters of blood make even mammography and colonoscopy unnecessary? What are the facts about the cancer blood test called liquid biopsy? On the occasion of World Cancer Day on February 4, experts from the German Cancer Research Center (DKFZ) report on the current state of research: What is already possible today and what can be expected of the cancer blood test in the near future?

© D.Anders/DKFZ

About a year ago, a California-based company called GRAIL announced a blood test to detect all conceivable types of cancer in healthy individuals. Market launch was expected for 2019. GRAIL is a spinoff of Illumina, the world's dominant manufacturer of DNA sequencing technology. This announcement received additional attention because Microsoft founder Bill Gates and Amazon founder and CEO Jeff Bezos are among the participating investors of the startup company.

The biological background of the test: Tumors continuously shed DNA as well as whole cancer cells into the blood. Their detection is called liquid biopsy. Each tumor has its own characteristic pattern of cancer-specific mutations. Today's advanced methods for ultrasensitive DNA analysis allow scientists to capture the cancer-typical DNA fragments – amongst all the other genetic material from healthy cells that are also floating in the blood.

"In many cases it is already possible to screen for tumor DNA in blood from cancer patients after treatment in order to monitor whether the cancer has returned," said Peter Lichter, the head of DKFZ's Molecular Genetics Division. "This has given rise to the new vision of also using blood tests for tumor DNA for early cancer detection in the future. But the hypothesis that underlies this vision yet has to be confirmed by data."

"Even if this kind of detection should turn out to be technically feasible one day," added Susanne Weg-Remers, the head of DKFZ's Cancer Information Service (KID), "it would still be necessary to prove, as for all early detection examinations, that people actually benefit from it, namely that it increases survival times or improves quality of life."

Tracking therapy response in the blood

Holger Sültmann, who leads the Cancer Genome Research Group at the DKFZ, thinks that it is just a question of time until blood tests for tumor DNA will receive clinical approval for use in cancer medicine. However, he adds that these will initially not be tests for early detection of cancer. The development of tests for monitoring therapy response in cancer cases that have already been diagnosed is presently far more advanced. "In contrast to tumor tissue biopsies, blood can easily be drawn several times at short intervals. Thus we can track whether and for how long the tumor responds to a cancer drug. This is important because cancer cells rapidly become resistant to many agents." Sültmann thinks that it is too early to tell when a DNA test for early cancer detection will be available.

Sültmann and his coworkers have studied in non-small cell lung cancer whether treatment response can be tracked by blood tests for tumor DNA. All patients in his study carried a particular cancer-driving mutation that had been detected in tumor tissue examinations prior to the study. This mutation indicates that the tumor is susceptible to a particular anticancer drug.

"We were able to observe clearly how the levels of cancer DNA in the blood dropped after treatment with this drug had started. And we saw that they increased again as soon as the tumor relapsed. Thus we confirmed an observation made in other studies that in the wake of an initially successful therapy, a new increase in tumor DNA levels in the blood is measurable three months earlier than other symptoms that are indicative of a relapse."

Many questions still have to be resolved before these tests will be ready for routine application: "For example, we do not know yet for how long tumor DNA is detectable in the blood or which time points are suitable for the blood tests."

According to Sültmann, the long-term goal is to use a blood test to identify the most effective drug for each individual patient without the need to analyze tissue from the tumor itself first. Many of the cancer-typical genetic alterations that liquid biopsies can detect are the key drivers of tumor growth. It would be possible to block them using targeted drugs, thus putting the brakes on cancer.

Whether or not this will work, and if it does, for which types of cancer, is not foreseeable at the present time, thinks Sültmann, and he sums up: "I expect that liquid biopsy will have a place in cancer medicine – for specific questions in specific cancer types. But there will be no general 'cancer test' in the foreseeable future."

Cancer cells in the blood determine the prognosis

A cancer patient's blood contains not only tumor DNA but also whole cancer cells. What information about the disease can be obtained by detecting these circulating tumor cells (CTCs)? "For many cancers it is well documented that the number of CTCs is closely linked to the prognosis," said Andreas Trumpp, who is head of DKFZ's Division of Stem Cells and Cancer and director of the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM). "However, the result for the individual patient is not very predictive yet; it is rather a statistical statement. Therefore, these tests have so far not been exploited much for therapy decisions outside clinical trials."

"However, a living cell can provide much more information than a mere DNA molecule, and from its analysis we can learn a lot about the process of metastasis," Trumpp said. "Since very recently it has been possible, for example, to grow CTCs that were isolated from patient blood in the Petri dish. If this were possible on a larger scale, we could use these patient cells to determine in quick tests which drugs the tumor cells are sensitive to." In one of his own research projects, the stem cell researcher could recently show for breast cancer that not the number of CTCs is crucial, but special "metastasis-inducing" cells instead are responsible for the spread of the disease.

However, Trumpp is convinced that a combined analysis of tumor DNA and CTCs provides the most comprehensive information about a tumor. He therefore wants to develop a test system that will combine these two detection methods.

"Some patients who call our service are afraid that their cancer may return and hope that this can be detected as early as possible by regular blood tests," says Susanne Weg-Remers of the Cancer Information Service (KID). "Others think that liquid biopsy might spare them an invasive removal of tumor tissue and ask themselves whether this might be an option for them. Unfortunately, almost all of these novel examination methods are still at a stage prior to clinical routine care and should only be employed for patients in clinical trials. The Cancer Information Service readily answers any questions about the current state of developments in this field by telephone or email at any time."

Phone (within Germany only): 0800 420 30 40

With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.

To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:

  • National Center for Tumor Diseases (NCT, 6 sites)
  • German Cancer Consortium (DKTK, 8 sites)
  • Hopp Children's Cancer Center (KiTZ) Heidelberg
  • Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
  • National Cancer Prevention Center (jointly with German Cancer Aid)
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.


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