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Updated: Nov 24, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Next Generation Sequencing-Based Profiling of Cell Free DNA in Patients with Advanced Non-Small Cell Lung Cancer:
Riziero Esposito Abate1, Daniela Frezzetti1, Monica Rosaria Maiello1
1Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy.
Abstract:
Lung cancer (LC) is the main cause of death for cancer worldwide and non-small cell lung cancer (NSCLC) represents the most common histology. The discovery of genomic alterations in driver genes that offer the possibility of therapeutic intervention has completely changed the approach to the diagnosis and therapy of advanced NSCLC patients, and tumor molecular profiling has become mandatory for the choice of the most appropriate therapeutic strategy. However, in approximately 30% of NSCLC patients tumor tissue is inadequate for biomarker analysis. The development of highly sensitive next generation sequencing (NGS) technologies for the analysis of circulating cell-free DNA (cfDNA) is emerging as a valuable alternative to assess tumor molecular landscape in case of tissue unavailability. Additionally, cfDNA NGS testing can better recapitulate NSCLC heterogeneity as compared with tissue testing. In this review we describe the main advantages and limits of using NGS-based cfDNA analysis to guide the therapeutic decision-making process in advanced NSCLC patients, to monitor the response to therapy and to identify mechanisms of resistance early. Therefore, we provide evidence that the implementation of cfDNA NGS testing in clinical research and in the clinical practice can significantly improve precision medicine approaches in patients with advanced NSCLC.
Insights
Next-generation sequencing (NGS) of cell-free DNA (cfDNA) offers a valuable alternative for non-small cell lung cancer (NSCLC) molecular profiling when tissue is insufficient, improving precision medicine.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Lung cancer (LC) is a leading cause of cancer mortality globally, with non-small cell lung cancer (NSCLC) being the most prevalent type.
- Tumor molecular profiling is essential for guiding targeted therapy in advanced NSCLC, but tissue inadequacy affects approximately 30% of patients.
- Circulating cell-free DNA (cfDNA) analysis using next-generation sequencing (NGS) presents a promising alternative for molecular profiling.
Purpose of the Study:
- To review the advantages and limitations of NGS-based cfDNA analysis in advanced NSCLC.
- To evaluate the role of cfDNA NGS in guiding therapeutic decisions, monitoring treatment response, and detecting resistance mechanisms.
- To highlight the potential of cfDNA NGS implementation in clinical practice for advancing precision medicine in NSCLC.
Main Methods:
- Review of current literature on NGS technologies applied to cfDNA analysis in NSCLC.
- Analysis of cfDNA NGS for assessing tumor molecular landscape, heterogeneity, and treatment monitoring.
- Evaluation of cfDNA NGS in comparison to traditional tissue-based biomarker analysis.
Main Results:
- NGS analysis of cfDNA is a sensitive method for molecular profiling when tumor tissue is inadequate.
- cfDNA NGS testing can better capture NSCLC tumor heterogeneity compared to tissue biopsy.
- cfDNA NGS facilitates therapeutic decision-making, response monitoring, and early detection of resistance mechanisms.
Conclusions:
- NGS-based cfDNA analysis is a valuable tool for precision medicine in advanced NSCLC, especially when tissue is unavailable.
- Implementation of cfDNA NGS testing in clinical research and practice can significantly enhance personalized treatment strategies.
- cfDNA NGS holds the potential to improve patient outcomes by enabling timely and accurate molecular-guided therapies.
