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Updated: Feb 9, 2026
A Standardized Liquid Biopsy Preanalytical Protocol for Downstream Circulating-Free DNA Applications
Published on: September 16, 2022
Abstract:
In the era of the personalized medicine, we need not only to an accurate diagnosis of lung cancer but also to assess the molecular pathways involved in order to target them. The most relevant targets in lung cancer are the genes EGFR, ALK-EML4, ROS1, Her2Neu, BRAF. Mutations or translocations of these genes are performed on biopsies in 80% of the cases and 30% of the patients cannot have their molecular tests done. This may be due to the lack of tumor samples secondary to the morphologic and immunohistochemical techniques, contraindication to biopsy or difficulties to biopsy. Besides, tumor cells tend to activate other pathways that weren't activated at the onset in order to escape to therapeutic drugs. This phenomenon of resistance is observed 3 to 6 months after the onset of the treatment. In order to escape all these limitations, liquid biopsy was developed. It consists in a simple blood sample of 5 to 10 ml in which circulating tumor cells, circulating tumor DNA, tumor RNA, exosomes and secretomes are explored. In this paper, we tried to define liquid biopsy, to highlight the means of diagnosis, its limits, its advantages and its perspectives in Tunisia.
Insights
Liquid biopsy offers a less invasive alternative for lung cancer molecular profiling, overcoming limitations of traditional tissue biopsies. This blood test analyzes circulating tumor DNA and cells for personalized treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Accurate lung cancer diagnosis and molecular profiling are crucial for personalized medicine.
- Key molecular targets include EGFR, ALK-EML4, ROS1, Her2Neu, and BRAF genes.
- Traditional tissue biopsies face limitations, with 30% of patients unable to undergo molecular testing due to sample inadequacy or accessibility issues.
Purpose of the Study:
- To define liquid biopsy as a diagnostic tool for lung cancer.
- To highlight the diagnostic methods, advantages, limitations, and future perspectives of liquid biopsy.
- To address challenges in molecular testing for lung cancer patients.
Main Methods:
- Exploration of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), tumor RNA, exosomes, and secretomes in blood samples.
- Analysis of molecular targets like EGFR, ALK-EML4, ROS1, Her2Neu, and BRAF.
- Comparison with traditional tissue biopsy methods.
Main Results:
- Liquid biopsy provides an alternative when tissue biopsy is not feasible.
- Identifies molecular alterations for targeted therapy selection.
- Circulating tumor components can be detected in small blood volumes (5-10 ml).
Conclusions:
- Liquid biopsy circumvents limitations of tissue biopsies in lung cancer molecular profiling.
- It offers a promising approach for personalized medicine and overcoming therapeutic resistance.
- Further research and implementation are needed, particularly in regions like Tunisia.
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