As the techniques that have enabled us to analyses and assess a biopsy become ever more sophisticated, we have realised the limitations of looking at the single snap-shot of the tumour. This single-biopsy bias was highlighted in which it was mainly demonstrated that a portion taken from different parts of a primary tumour and its metastases showed and proved extensive intertumoural and intratumoural evolution. This tumoural heterogeneity mainly highlights the difficulty of dictating a therapeutic course of action based on the single biopsy, as it is likely to underestimate the ramification of the genomic landscape of the tumour (Chomczynski et al., 2016).Having established that there is mainly considerable tumour heterogeneity, taking multiple biopsies from the patients‘ primary tumour and the metastases would seem to be the most obvious next step. There are so much difficulties in obtaining the tissue biopsy— including the discomfort suffered by the patient, the inherent clinical risks to the patient

1. B Y D R . S . S R E E R E M Y A
F A C U L T Y O F B I O L O G Y
Liquid Biopsies – An
Overview

2.  INTRODUCTION
 As the techniques that have enabled us to analyses and assess a biopsy
become ever more sophisticated, we have realised the limitations of looking
at the single snap-shot of the tumour. This single-biopsy bias was
highlighted in which it was mainly demonstrated that a portion taken from
different parts of a primary tumour and its metastases showed and proved
extensive intertumoural and intratumoural evolution. This tumoural
heterogeneity mainly highlights the difficulty of dictating a therapeutic
course of action based on the single biopsy, as it is likely to underestimate
the ramification of the genomic landscape of the tumour (Chomczynski et
al., 2016).Having established that there is mainly considerable tumour
heterogeneity, taking multiple biopsies from the patients‘ primary tumour
and the metastases would seem to be the most obvious next step. There are
so much difficulties in obtaining the tissue biopsy— including the
discomfort suffered by the patient, the inherent clinical risks to the patient

3.  In addition, some tumours are not accessible for biopsy, the procedure
itself might aggrandize the risk of the cancer ‗seeding‘ to other sites, and
the procedure and the steps might not be recommended for the patients
receiving antiangiogenic treatment(Mandel et al.,1948).
 Even in an ideal situation where several Meta static sites can be mainly
biopsied simultaneously, the analysis of the samples can majorly delay the
initiation of treatment, and might irremediably jeopardise it (Schutz et al.,
2014). These limitations are specific restraints in the setting of the acquired
resistance to therapy, as the ability of a clinician to detect therapeutic
biomarkers at an early stage would allow the potentially successful change
in treatment course. In light of these limitations on the use of the single
biopsies, new ways to observe tumour genetics and tumour dynamics have
evolved. In 1949, the publication of a manuscript that delineated
circulating free DNA (cfDNA) and RNA in the blood of humans was,
without knowing it, the first step towards the path breaking medical
procedure termed ‗liquid biopsy‘(Fawzy et al.,2016).

4.  The liquid biopsy was first applied in the year1869 by the pathologist
Thomas Ashworth, who showed the existence of the circulating tumor cells
(CTCs) in the blood of a patient with metastatic cancer. Tumor cell masses,
as well as the normal tissues, shed components such as whole cells known
as CTCs, the cell-free nucleic acids (cf-nucleic acids) and extracellular
vesicles (EVs), which end up in the bloodstream or the other body fluids
depending on their place of origin. These tumor components are targets of
the biomarker search that may enable to monitor tumor development.
Thus, any sample from the body fluid encompassing these targets is termed
liquid biopsy (Salvi et al., 2015). Biopsies are major sample analysing
techniques (Sreeremya, 2019a). Current researches are going on regarding
the diagnosis of prostate cancer in dogs by liquid biopsies (Sreeremya,
2019b).
 The prostate specific antigen (PSA) is the gold standard biomarker for the
bioclinical manage-ment of the prostate cancer (PCa). However, the PSA
shows a low accuracy, with a high rate of false-negative and the false-
positive results

5.  Although PSA is a circulating glycoprotein detected and
assessed in blood serum samples and can be considered
as the liquid biopsy itself, a positive result in PSA (high
serum levels) needs a confirmation through histological
examination of the surgical prostate biopsy from the
patient. In an attempt to find much more effective and
less invasive clinical tool for PCa, researchers from all
over the world are developing the novel strategies based
on liquid biopsies from the blood, urine, seminal fluid
and stool (Krebs et al., 2014).
 CTCs are rare cells from primary and the metastatic
tumors that circulate throughout the body to form
metastatic niches in the other tissues.

6.  These cells are detectable in cancer patients while they are undetectable in the healthy
individuals. Since CTCs may mainly derive from different tissues, they constitute the
heterogeneous population of cells that represents a comprehensive view of the cancer
progression in a patient (Labelle et al., 2011). CTCs are released into blood, but the CTCs from
PCa can be also found with the high probability in urine, seminal fluid or the stool because of
their organ of origin. Nucleic acids contained in CTCs, which allow monitoring the epigenetic
and genetic alterations, proteins expressed on the surface or inside CTCs, as well as the number
of these CTCs are biopotential cancer biomarkers (Le Gal et al., 2015).
 Due to the genetic diversity and the rapidly changing the dynamics of genomic profiles among
cancer patients, the better treatment efficacy could be attained if cancer therapeutics could shift
from the concept of ‗one-size-fits-all‘ approach to an individual level tailored treatment
strategy . Precision oncology is expected to typically emerge as an initiative to tackle various
obstacles faced in the cancer management, such as unexplained drug resistances, genomic
heterogeneity of the tumors and lack of appropriate methods for monitoring the responses to
therapies (Park et al., 2016). One of the prime challenges for the bioclinical implementation of
precision oncology is to identify and detect molecular biomarkers that could predict the
prognosis, the sensitivity or resistance to a specific single agent or combination therapies, or
specific therapy-allied adverse drug reactions. In this scenario, the liquid biopsy has been
recently gaining widespread attention globally as an alternative/complementary to the tissue
biopsy in the era of ―cancer theranostics‖

7. REFERNCES
 Journal of Research in Medical and Surgical
Nursing,Liquid biopsies-An overview,
Dr.S.Sreeremya ,2020.Vol 2(1):1-6.