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E. Heitzer. Point: Circulating Tumor DNA for Modern Cancer Management Clin Chem 2020;66:143–145.
J.Y. Pierga. Counterpoint: Circulating Tumor Cells for Cancer Management Clin Chem 2020;66:146–148.
Professor Klaus Pantel is Chairman of the Institute of Tumor Biology at the University Medical Center in Hamburg-Eppendorf in Germany.
This is a podcast from Clinical Chemistry, sponsored by the Department of Laboratory Medicine at Boston Children’s Hospital. I am Bob Barrett.
Molecular diagnostics is the topic of the January 2020 special issue of Clinical Chemistry. In that issue, there is a counter point report on the use of circulating tumor cells in the management of cancer patients. To provide further insight on this topic, we’re joined in this podcast by one of the editors of this special issue. Professor Klaus Pantel is Chairman of the Institute of Tumor Biology at the University Medical Center in Hamburg-Eppendorf in Germany. So, Dr. Pantel, what are the current clinical applications of circulating tumor cells?
Well, the first application is really the risk assessment for patients that has been newly diagnosed with cancer and particularly, patients with solid tumors such as breast cancer, prostate cancer, colon cancer, or lung cancer. And particularly in breast cancer, the number of tumor cells that we find in newly diagnosed patients is a significant indicator of the risk to develop a metastatic relapse in the next 5 to 10 years.
The second application where we can use it is to monitor the efficiency of therapies and, here, we can take blood samples within six weeks after the start of chemotherapy in breast cancer patients, for example. And we get -- depending on the increase or decrease of the CTC counts in these patients-- a idea whether therapy is working or it’s going in the wrong direction. And here, we have data for breast and prostate cancer. And in prostate cancer and particularly in the castration resistant patients, the early reduction of the circulating tumor cells indicate that the therapy is working and the early increase in the number of tumor cells indicating that the therapy is not working.
For monitoring the blood samples during the treatment and getting the information on whether the CTC counts increase or decrease or remain unchanged gives an early information on whether the therapy is working in individual patients or not.
Well that sounds wonderful, but there must be challenges. What are they?
The challenge actually is that there are certain patients even with metastatic disease, who have no CTCs in their blood or who have a very lower number of circulating tumor cells. And also, this is a good prognostic sign meaning that these patients have a longer time before progression is being observed. It bothers us because we would like, of course, to further characterize circulating tumor cells and particularly in metastatic patients to learn about therapeutic targets or therapeutic resistance mechanisms. And if you don’t find circulating tumor cells in let’s say, 20% to 30% of those patients, then we cannot get this information. And that of course still a challenge. So we need to make these assays more sensitive or try other methods to capture more circulating tumor cells out of the blood sample.
What are the latest innovations and trends and advances in this field?
Well, one of the latest innovations and trends is really trying to capture many circulating tumor cells as possible by doing some in vivo capturing, which means actually placing a needle into the blood vein and then trying to capture as many tumor cells as they flow through the vein as possible. And some of these devices has been tested already in cancer patients and some of these devices has been introduced in animal models. So that’s one of the latest developments.
Another latest development is that we try to use the leukapheresis, which means we wash the whole blood so that we get all the tumor cells that are circulating at a given time out of the blood, and that also gives us access to hundreds of circulating tumor cells, which of course increases our ability to further analyze these cells.
What are the benefits for the clinician and the patient for using this?
Well, a clear benefit in my view is, of course, if we can use this to get an early indication whether a therapy works or not, we may switch to another therapy before it’s too late. And I think one can imagine that if you wait too long, that the tumor burden in the individual patient may increase exponentially. And if you switch too late to another therapy, it would be impossible to change the course of the disease.
So using the CTCs as an early indicator of treatment response would give us probably the ability to act earlier, and with the hope that the next therapy that we then select would be more efficient than the first one.
Well finally, doctor, let’s look ahead. What does the future hold for liquid biopsy? Where’s the next innovation?
Well, the next level of innovation is certainly in the molecular characterization of circulating tumor cells. We have already entered that avenue. We are able to do a single-cell genomics and also single cell transcriptomics. But I think there will be more and more sophisticated technologies that become available to do the single-cell circulating tumor cell, and this is at a larger scale. And that will give us more information about the molecular make-up of the circulating tumor cells.
Also, in particularly, with the expression of therapeutic targets or therapeutically used pathways and also with the information on potential resistance mechanisms that may allow us to switch from one drug to the other. So the future is definitely in analyzing and characterizing these circulating tumor cells to get more information that we can use for drug treatment as a companion diagnostics.
That was Professor Klaus Pantel, the Chairman of the Institute of Tumor Biology at the University Medical Center in Hamburg-Eppendorf in Germany. He has been our guest in this podcast on the use of circulating tumor cells in the management of cancer patients. Dr. Pantel is one of the guest editors for the January 2020 issue of Clinical Chemistry focusing on molecular diagnostics. I’m Bob Barrett. Thanks for listening.