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Luis Enrique Cortés-Hernández, Zahra Eslami-S, and Catherine Alix-Panabières. Liquid Biopsy to Detect Circulating Tumor Cells: Is It Ready for a Value Proposition in Laboratory Medicine?. J Appl Lab Med 2020;5:1027-37.
Mr. Luis Enrique Cortes-Hernandez and Ms. Zahra Eslami-Samarin are Marie Sklodowska-Curie Fellows at the University Medical Center of Montpellier, France.
Hello, and welcome to this edition of “JALM Talk” from The Journal of Applied Laboratory Medicine, a publication of the American Association for Clinical Chemistry. I’m your host, Randye Kaye.
Cancer is a complex and heterogeneous disease. The diagnosis and staging of cancer are often based on the results of a tissue biopsy that only provides a small fraction of the whole tumor mass. Obtaining a tissue biopsy involves an invasive procedure and it’s often not safe or feasible to monitor a patient’s disease over time with this method. For these reasons, the ability to detect and routinely monitor cancers via a minimally invasive blood test, or a so-called liquid biopsy, is an attractive alternative.
A Review article in the September 2020 JALM Special Collection on the value of laboratory testing and the value proposition examines the current state of circulating tumor cell analysis as a liquid biopsy. The authors identify the gaps and unmet needs for future implementation into clinical practice. The co-first authors of the article are Luis Enrique Cortes-Hernandez and Zahra Eslami-Samarin. Mr. Cortes-Hernandez and Ms. Eslami are Marie Sklodowska-Curie fellows at the University Medical Center of Montpellier, France. They are researchers at the Laboratory of Rare Human Circulating Cells under the supervision of the senior author of the article, Dr. Catherine Alix-Panabieres. Mr. Cortes-Hernandez and Ms. Eslami are both joining us for this podcast. Welcome! What is meant by the term “liquid biopsy” and how can circulating tumor cells, or CTCs, be used as a liquid biopsy?
Luis Enrique Cortes-Hernandez: Well, in cancer basically, the liquid biopsy term describes the minimally invasive analysis of analytes released by or related to the primary and/or metastatic tumors. These analytes can be found in any physiological or pathological body fluids; many are found in blood. Liquid biopsy is an extension of tissue biopsy, and many cancer biomarkers of clinical utility can be translated from tissue to liquid biopsy. Additionally, new biomarkers can be easily identified in liquid biopsy analytes because they are thought to represent more accurately cancer progression, and it is inter- and intra-tumor heterogeneity. Some examples of liquid biopsy analytes are secretory tumor cells, circulating free nucleic acids such as circulating free DNA or circulating free RNA, exosomes, vesicles, and tumor-educated platelets more recently. CTCs are the main drivers of the metastatic state. These analytes hold biomarkers that are already described in tumors, but with the clear advantage to make a real-time follow-up of the evolution of such marker during treatment.
Thank you. So, how prevalent are CTCs in patients with cancer and how can we capture them, so there is enough to measure?
Well, CTC are very uneven and their number in blood sample will vary depending on the cancer type or subtype. For example, the cut-off in the number of CTC in breast cancer to have a prognostic value is 5 CTC in 7 .5 ml of the plot. This is significantly low when you compare with other cells in blood leukocyte or erythrocyte. There are many strategies and methods to isolate or enriched CTC from blood. So far, only one method has been cleared by FDA for the enumeration of CTC in breast, prostate, and colorectal cancer, which is based on enrichment of epithelial CTC by the expression of EpCAM surface marker. Of course, this method has limitation, as CTC is not always expressed EpCAM and they will be lost for the analyzers. Other methods based on the physical properties or other marker in different stage of development be very promising opportunity for the field to overcome limitation to capture more CTC out of blood samples.
Thank you. You may have already answered this a little bit, but maybe we can elaborate on, where does the field of CTC stand today? Are there any current clinical applications?
Luis Enrique Cortes-Hernandez:
Well, so far, the clinical validity and prognostic value of CTCs evaluated with this EpCAM based methods is already accepted. However, there’s still work need to do to find a clear clinical utility. This means that the enumeration or identification of biomarkers in CTCs can change their unhealthy behavior in a patient. So far, we can use CTCs to monitor the efficacies of therapies. For instance, in breast cancer and prostate cancer, we can evaluate an increase or decrease of CTCs after beginning chemotherapy and also even predict which treatment could offer better outcomes before the start of the treatment. Current ongoing clinical trials are very promising to answer these questions; however, still it is important to note that more intervention and clinical trials are needed to identify all clinical scenarios in which CTCs could offer benefits.
I want to mention that your article is actually part of a JALM Special Collection, which is called Value of Laboratory Testing and the Value Proposition. So, keeping this in mind, in your opinion, what is the value of CTCs in laboratory medicine?
Well, still it’s not possible to establish a clear value of CTC in laboratory medicine. There is an immediate need for more evidence of clinical utility and health economic evaluation. This evidence can lead to the further acceptance for the funding agency in the health care system; however, this is an ongoing process, even though only one method has success to go further and find clinical utility. The current development of other alternatives to analyze CTC will probably lead to the identification of new clinical scenarios in which CTC analytes can influence for better outcomes in patients with cancer.
All right. Thank you. And once again, you have touched upon this. Anything else to say about what you think the future will hold for CTCs and liquid biopsies?
Luis Enrique Cortes-Hernandez:
Yes, liquid biopsy is a field that has exponentially grown in the last years. For instance, there has been an increase of private and public agencies’ involvement in the funding of research in this field. Some examples are the European Liquid Biopsy Academy and the European Liquid Biopsy Society that are supported by the European Union. In this collaborative and international context, basic and clinical studies have shown that different analytes of liquid biopsy might be superior to each other depending on the cancer type, anatomical location, therapeutic agents used, and stage of the cancer. In the future, the different analytes of liquid biopsy should be selected or combined in according to the best clinical outcome. It is interesting to make an analogy to the current approach of tissue biopsy, as this is not just a single method; instead diagnostic methods should be and are selected accordingly to the clinical patient context and liquid biopsy should not be the exception. CTCs will be a fundamental part of the future of liquid biopsy, and it is a guarantee that as more methods are developing and approved for their analysis, more chances to integrate their analysis in the common cancer clinical care of patients, and not to forget that CTCs are the drivers of metastasis. So, future therapeutic agents against these cells my offer a whole new type of therapeutic approaches.
Well, thank you. That’s very interesting and very exciting. Thank you for both of you for joining us today and for your time.
Luis Enrique Cortes-Hernandez:
Thank you, too.
That was Luis Enrique Cortes-Hernandez and Zahra Eslami-Samarin from the University Medical Center of Montpellier describing the JALM Review article “Liquid Biopsy to Detect Circulating Tumor Cells: Is it Ready for a Value Proposition in Laboratory Medicine?” Thanks for tuning into this episode JALM Talk. See you next time and don’t forget to submit something for us to talk about!