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EDITORIAL

Liquid Biopsy: Opportunities and Expectations
Rizwan Hashim

Introduction
Tumors have an abnormal rate of cell growth and cell 
division. Tumor cells release circulating tumor DNA 
(ctDNA), cell free DNA (cfDNA), mRNA and 

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microRNA,  in the blood and body fluids which are 

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the by-product of tumor cell lysis.  Both ctDNA and 
cfDNA provide valuable information regarding the 
cancer related mutations, genetic aberrations and 

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presence of cell free Nucleic acid (cfNA).  The ctDNA 
provides information about the primary tumor and 
its secondaries / metastases. It is these ctDNA that 
anchor into novel locations and start dividing to 

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develop secondaries of the tumours.
Tumor biopsy is an invasive procedure in which tissue 
is excised from a growth and examined under a 
microscope. However, “Liquid Biopsy” is a relatively 
newer technique to find and evaluate cancer cells or 
their products in blood and body fluids that circulate 
after tumor cell lysis. 
Historical Aspect for the Use of Liquid Biopsy:
The basis of liquid biopsy was the observation made 

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by Ashworth  in 1869, where the circulating tumor 
cells were detected in a patient with tumor 
secondaries. The metastatic sites also shed tumor 
cells in the blood stream that could be detected and 
analyzed. It was after a long gap when scientists 
realized that the cell free DNA (cf DNA) could be 
detected, analyzed, and quantified. It was in 1948 
when cell free DNA and free RNA was first detected 

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and quantified.  This was done both in healthy 
individuals and those who had cancer. Progressing 
forward, it was in 1966 the researchers detected 
large volumes of cell free DNA in patients who had 
lupus. By 1980 the cell free DNA was also detected 
among oncology patients. In 1994 the scientists 
started detecting specific mutations from the cell 

free DNA present in the blood of oncology patients 
®

and by 2000 Veridex introduced CELL SEARCH  CTC 
test, for liquid biopsy assay as a first commercially 
available test for liquid biopsy, however CAPP Seq: 
cancer Personalized profiling by deep sequencing is 
another method for quantifying ctDNA analysis that 

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is being used.  The Cobas  EGFR was the first liquid 
biopsy test that was approved by FDA in 2016.  This 
test was for EGFR gene mutation to be detected in 

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blood drawn from cancer patients.  Nowadays, 
ctDNA and cfDNA can be analyzed commercially by 
Mag Max Cell Free DNA Isolation kits and Cell Free 
Nucleic Acid Isolation Kits used for liquid biopsy 

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specimens.
Applications and Advantages of the Liquid Biopsy 
Technique:
When blood/body fluids are drawn as liquid biopsy 
for ctDNA and cfDNA, they also contain membrane 

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bound lipid globules called Exosomes.  They contain 
tumor proteins, lipids, DNA fragments and micro 
RNA. The tumor related material in the exosomes 
can be analyzed to provide information about the 
mechanism involved in signals between the tumor 
cells, especially between primary tumors and 
metastatic sites. This is one of the many novel 
features of liquid biopsy and is not achieved by 
conventional tissue biopsy. Liquid biopsy provides a 
window of opportunity to understand tumor cell 
signaling that can be manipulated by various 
treatment modalities for cancer management. As 
cancer is a complex problem with systemic effects, 
liquid biopsy with frequent sampling provides a 
unique chance for mutation characterization and 

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exosomal analysis.
Together, these analytes have the strength to give 
the details of the tumors genetics, its metastasis and 

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various stages of tumor progression.  The 
information provided is used for: genomics, 
e p i ge n o m i c s ,  t ra n s c r i p to m i c s ,  p ro te o m i c s ,  
metabolomics and information regarding minimal 

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residual disease.   The major oncology domains 
where liquid biopsies have been successfully used 

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are: colorectal,   breast and lung cancers, mainly to 
predict therapy responses and to monitor the 

Correspondence:
Prof. Dr. Rizwan Hashim
Fazaia Medical College,
Air University Islamabad
E-mail: riznajmi20011@hotmail.com

Received: July 16, 2020; Accepted: November 11, 2020

Department of Pathology
Fazaia Medical College,
Air University Islamabad



Acknowledgement 
1. No conflict of interest is declared.
2. No financial assistant or grant was provided.
3. No endorsement of any device / Kit / 

manufacturer or technology is implied.

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resistance.  Moreover, with quantum leaps in 
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analysis. 

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