Klaus Pantel (Bergisch Gladbach, Germany, 63 years old) began chasing migrating cancer cells through the bloodstream 30 years ago. After years of work, Pantel was able to identify that patients with a high number of those cells died earlier, and in 2010, together with Catherine Alix-Panabièresfrom the Montpellier University Hospital Center (France), wrote an article in which they explained the potential of detecting tumor cells in the blood for the early discovery of tumors and their monitoring. There the term liquid biopsy arose, the idea that with a blood test, without having to extract cancerous tissue from the patient, it would be possible to know if they had the disease.
“The term was adapted very quickly to talk about the detection of products circulating in the blood, from tumor cells to circulating DNA; “We had no idea that it was going to be so popular,” acknowledges Pantel, director of the Hamburg Institute of Tumor Biology, who a few days ago visited the National Cancer Research Center (CNIO) in Madrid. Now, liquid biopsy is one of the most promising tools to detect cancer when it is still treatable, to design personalized therapies or to evaluate whether a treatment is working or if it should be changed.
Ask. How did you come up with the idea of doing a liquid biopsy?
Answer. We were thinking about getting as much information from a cancer patient’s blood as possible. Usually, to obtain information about a tumor, you take a syringe and puncture the tumor tissue. That’s a tissue biopsy and we thought we could do that with blood. And because we thought “blood biopsy” didn’t sound right, we called it liquid biopsy.
Q. Is the name important for a medical procedure to be accepted?
R. The name is very important. There were other groups that proposed other names, but this one survived.
Q. What are the obstacles that liquid biopsy still has to be a commonly used diagnostic method?
R. The challenge right now is to take it from research to clinical practice. To achieve this, we have to ensure that the blood tests we use are robust and work, and that they work the same on a Monday as on a Friday, so that we can standardize the technology. It is also important that we develop the appropriate tests for each clinical question. For example, if you want to detect pancreatic cancer early, you need very sensitive tests to detect the tumor when it is small and there are very few molecules in the blood. But if you have a tumor in the metastatic phase, with advanced disease, there are more molecules in the blood and you can do another type of analysis. And you also have to choose which patients can benefit from each type of test and make it available to doctors. It is a mix of clinical validation, technology and also education of specialists.
For now, liquid biopsies are most useful for tracking how treatment is working, because it is a painless test that you can do, if necessary, every day. This way you can see if an individual is responding to a therapy, if the tumor burden is going up or down, or if the cancer is developing resistance to treatment. The tests also tell us the molecular characteristics of the tumor and consider which therapy may be most appropriate.
Q. Can other screening systems used now replace these types of tests?
R. It can be used to screen for lung cancer or pancreatic cancer, which is detected when it is too late and the tumor is too large. That would be a big help to patients, because surgeons could remove the tumor while it is still small. Another project we have now, and which we have talked about in the CNIO, tries to follow up after the tumor has been removed. At that point, you may think you’re safe, but tumor cells may continue to spread, even though the radiologist can’t see them. The question that all patients have is: Is my tumor coming back or am I cured? With these blood tests, we can find signs of the tumor coming back months before the radiologist can see it. And if I can do that, in the future, I could give therapy sooner.
Q. What would those very early treatments be like, like a blood pressure pill that keeps those tumor cells circulating in the blood at bay?
R. Yes, the best would be a pill, because it is easy to take, and ideally it would not have many side effects so that it can be taken as prevention, eliminating those tumor cells from the blood or keeping them at very low levels. The question is what kind of medication could help stop the disease at this early stage.
Q. Early detection also has risks of overdiagnosis or failing to reduce cancer deaths, as has been seen with mammograms.
R. If you use this technology to detect tumors, you have to make sure [de que ese material circulante] It’s from a tumor, because if not, you drive the patients crazy. The tests have to be very precise, because if not, you terrify people.
Q. Is there any type of tumor in which liquid biopsy is more interesting?
R. The most common are breast, colon and lung, but also aggressive tumors such as pancreas or ovary, which are always detected too late. There is a great medical need there.
Q. Is it also of interest as a research tool, to understand how tumor cells travel through the body and jump from one organ to another?
R. I have been working on tumor cell metastasis for more than 30 years and we have seen that these cells spread throughout the body at a very early stage of tumor development. Before we thought that the tumor had to be large to spread, but not all the cells that travel grow. Some can be silent for more than ten years, such as breast cancer. The body can control the spread of cancer all that time, but the key is why that control system stops working. In breast cancer you can have relapses after 15 years. Understanding how the body controls tumor cells is very important, because it could be used in new therapies.
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