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)