Hunting for the ultimate liquid cancer biopsy - let the TEP dance begin

Cell Communication and Signaling, Sep 2016

Non-protein coding RNAs in different flavors (miRNAs, piRNAs, snoRNAs, lncRNAs, SHOT-RNAs), exosomes, large oncosomes, exoDNA and now tumor-educated platelets (TEPs) have emerged as crucial signal transmitting, transporting and regulating devices of cells in the last two decades. They are also establishing themselves increasingly in the realm of tumor research. We are currently witnessing a mushrooming of candidate entities for diagnostic and prognostic cancer detection and characterization tests that could have a major impact on how this diverse group of diseases is initially spotted and subsequently treated in the near future. But how do the new kids on the block stand up to the more established circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)? Without question, much earlier disease detection would be expected to save numerous lives. With all these new players around, will we finally win a major battle in the never-ending war against cancer?

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Hunting for the ultimate liquid cancer biopsy - let the TEP dance begin

Feller and Lewitzky Cell Communication and Signaling Hunting for the ultimate liquid cancer biopsy - let the TEP dance begin Stephan M. Feller 0 Marc Lewitzky 0 0 Institute of Molecular Medicine, Martin-Luther-University Halle-Wittenberg , Halle (Saale) , Germany Non-protein coding RNAs in different flavors (miRNAs, piRNAs, snoRNAs, lncRNAs, SHOT-RNAs), exosomes, large oncosomes, exoDNA and now tumor-educated platelets (TEPs) have emerged as crucial signal transmitting, transporting and regulating devices of cells in the last two decades. They are also establishing themselves increasingly in the realm of tumor research. We are currently witnessing a mushrooming of candidate entities for diagnostic and prognostic cancer detection and characterization tests that could have a major impact on how this diverse group of diseases is initially spotted and subsequently treated in the near future. But how do the new kids on the block stand up to the more established circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)? Without question, much earlier disease detection would be expected to save numerous lives. With all these new players around, will we finally win a major battle in the never-ending war against cancer? - Background Highly effective early cancer detection could save a huge number of patients from devastating, marginally effective therapies that are commonly accompanied by morbidity and/or followed by early death. Discovering tumors very early on, ideally before metastasis sets in, has therefore been on the minds of many cancer researchers and health care providers alike. After all, it is metastasis that kills the vast majority of cancer patients [1]. Cancers typically start from a single cell. However, with our present day routine methods this single cell usually will have multiplied into a billion or more cancer cells and often will have also evolved into several distinct subclones before the tumor is finally detected. It is commonly through patient observations and not specific medical tests that initial cancer signs emerge, for example in the form of a lump or some sort of pain. This then sets into motion a series of histological and/or molecular tests to determine the tumor origin and possibly even the disease subtype. Apart from the somewhat disputed successes of large scale routine mammographies [2], as well as visual skin inspections and Pap smears, current medical practice has fairly little to offer in terms of non- or minimalinvasive early cancer detection procedures. Manual prostate inspection and PSA determination are fairly crude tools that seem to have no substantial impact on prostate cancer survival rates [3, 4]. Endoscopic inspections of the aerodigestive tract could probably contribute to a significant boost in survival rates of some cancer types, but are by and large ignored as routine screening options for eligible individuals. They come with a low but non-negligible risk resulting from mechanical damages (bleeding, perforation) and anaesthetization complications (for more details see http://www.bsg.org.uk/ pdf_word_docs/complications.pdf ). Simple, robust analyses of body fluids like blood, saliva and urine would therefore be a quantum leap forward in our probably infinite quest to improve cancer survival rates. These ‘liquid biopsies’ [5], would have to detect cancer cells or their various products with great reliability to provide a practical, convenient and possibly only moderately costly expansion of our limited present day repertoire of cancer detection methods. Until now, such new test forms are mostly under development in various research laboratories and not widely applied in routine medical practice. This might, however, change in the next years. There are many candidates in the form of molecules and macromolecular assemblies to be considered, which could drive these changes. © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Main text Cells and extracellular vesicles The first category of candidates are the by now ‘classical’ circulating tumor cells (CTCs) [6, 7] and circulating DNA fragments (ctDNAs) [8, 9]. They are currently explored in several dozen clinical studies (see e.g. ClinicalTrials.gov for most recent details). Probably the most exciting new development in this area is the very recent finding that ctDNA seems to have a major role to play as a prognostic marker of surgery success of stage II (...truncated)


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Stephan Feller, Marc Lewitzky. Hunting for the ultimate liquid cancer biopsy - let the TEP dance begin, Cell Communication and Signaling, 2016, pp. 24, 14, DOI: 10.1186/s12964-016-0147-9