Long time ago it was wrongly thought that tumor genes and cells
are only existence in the exact tumor site. In spite of the fact of the
hypothesis that circulating tumor cells (CTCs) are a fundamental
prerequisite to metastasis ( first projected in the 1896 by Thomas
Ashworth, an Australian pathologist, ) and the presence of cfDNA
report in human plasma by Mandel and Metals in 1948, liquid
biopsy were totally ignored till 1977. In 1977, researchers made
the novel observation that cancer patients carried cell-free DNA
in their peripheral blood which was Initial progress on further of
liquid biopsy. Without a doubt, significant progress was not made
until recent years with the advent of Next Generation Sequencing
(NGS) technology, which significantly improved the sensitivity and
specificity of ctDNA detection. Interestingly, research in this field of
liquid biopsy has entered a “golden age” in which the huge potential
of liquid biopsy main components including CTCs, cfDNA and
exosomes make tumor diagnosis and treatment much clearer than
before. Liquid biopsy tests are fast traction as a viable substitute
to traditional diagnostic tests for cancer. It has the potential to
facilitate detect cancer at earlier stages, present a less-expensive
and less-invasive way to monitor patients throughout treatment,
and can help doctors make better decisions about which drugs are
the best fit for personal patients.
The questions are now:
a) We know all about liquid biopsy components?
b) Is there any possibility that we still are missing a main
representative of tumor genetics?
c) If the answer is yes what could be that components: RNA,
DNA, or cell?
Answering to these questions is not easy but it is supposed to
keep this question in mind. By way of illustration, in molecular
biology covalently closed circular DNAs are able to pass through
double layer of eukaryotic cellular membrane. Very recently the
presence of circular extra chromosomal DNA (ecDNA) has been
shown by Turner KM [1] which is different in seventeen different
types of cancers. In fact, ecDNA are the tricky way of oncogenes to
increase their copy number. It can be imagine that the presence of
ecDNA in the blood of cancer patients as a subpopulation of liquid
biopsy can be possible. On the occasion of their presence in blood
they will be very beneficial to cover the small amount of cell frees
DNA (cfDNA). Isolation and characterization of ecDNA will be
possible by a sensitive method entitled Circle-Seq. The origin of
tumor more than its prognosis and diagnosis will be possible in the
easiest way by using ecDNA as a liquid biopsy component. Thanks
to the latest breakthroughs in gene sequencing techniques all liquid
biopsy components will be discovered and determined within next
decade.