In the note below, we shall be discussing in brief about liquid biopsy in cancer under the following headings.
Definition
It is sampling and analysis of nonsolid biological tissue, primarily blood, to inform management.[1]
Need of Liquid Biopsy
There is a need of a technique that can complement or replace the traditional tissue biopsy overcoming the disadvantages and/or limitations associated with it.
Liquid biopsy:
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Offers the same simple, noninvasive, and faster than traditional biopsy.
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Allows assessment of intratumor heterogeneity, monitor tumor dynamics, and study tumor dormancy.
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Problems of tissue inadequacy are avoided as a few copies of mutant DNA are sufficient.
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Allows for serial evaluation ([Fig. 1]).[2]
Fig. 1 Advantages of liquid biopsy.
Types
Cancer cells shed intact cells as well as their cellular components (nucleic acids, exosomes) and with advancement in the laboratory techniques these can be isolated and analyzed ([Fig. 2]).[2]
Fig. 2 Types of liquid biopsy.
Circulating Tumor Cells
Cancer cells shed tumor cells into peripheral circulation mainly because of physical forces such as tumor growth, invasion of vessels rather than through epithelial mesenchymal transition that is an important mechanism in the development of metastasis.[3]
[4]
Tumor-Educated Platelets
Several normal cells form a part of the tumor microenvironment. The interaction of these cells with tumor affects not only the gene expression in the tumor but also RNA expression in the platelets. Such platelets are called as tumor-educated platelets.[6]
Methodology
It involves
Sample collection
↓
Isolation of circulating tumor cells (CTCs) and/or cellular components (nucleic acids, exosomes) by various enrichment techniques*
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Isolated CTCs and/or ctDNA are analyzed further through wide variety of applications such as NGS, polymerase chain reaction, or fluorescence in situ hybridization to look for copy number, mutations, translocations, amplification, deletions, chromosomal abnormalities, RNA expression, fusion transcripts, protein expression, and phosphorylation and culture and data obtained from it is analyzed and interpreted.
*Several enrichment techniques used are positive selection using antibodies against epithelial markers, negative selection using anti-CD45 antibodies that will remove the white blood cells, and other mechanical methods like filtration are used.[3]
[4]
Future Implication
Liquid biopsy is emerging as an important noninvasive technique that has both diagnostic and prognostic value. It is currently limited in routine use by the lack of convincing data to replace the traditional tissue biopsy. However, with rapid advancements in the enrichment and isolation procedures, liquid biopsy represents an important prospect because of its many advantages.
