Application of Circulating Tumor DNA as a Biomarker for Non-Small Cell Lung Cancer

Abstract

BackgroundNon-small cell lung cancer (NSCLC) is one of the most prevalent causes of cancer-related death worldwide. Recently, there are many important medical advancements on NSCLC, such as therapies based on tyrosine kinase inhibitors and immune checkpoint inhibitors. Most of these therapies require tumor molecular testing for selecting patients who would benefit most from them. As invasive biopsy is highly risky, NSCLC molecular testing based on liquid biopsy has received more and more attention recently.ObjectiveWe aimed to introduce liquid biopsy and its potential clinical applications in NSCLC patients, including cancer diagnosis, treatment plan prioritization, minimal residual disease detection, and dynamic monitoring on the response to cancer treatment.MethodWe reviewed recent studies on circulating tumor DNA (ctDNA) testing, which is a minimally invasive approach to identify the presence of tumor-related mutations. In addition, we evaluated potential clinical applications of ctDNA as blood biomarkers for advanced NSCLC patients.ResultsMost studies have indicated that ctDNA testing is critical in diagnosing NSCLC, predicting clinical outcomes, monitoring response to targeted therapies and immunotherapies, and detecting cancer recurrence. Moreover, the changes of ctDNA levels are associated with tumor mutation burden and cancer progression.ConclusionThe ctDNA testing is promising in guiding the therapies on NSCLC patients.

The Role of Circulating Biomarkers in Lung Cancer

“…The United States Food and Drug Administration (U.S. FDA) approved ctDNA as the first liquid biopsy test for the detection of NSCLC patients with EGFR mutations who were suitable for personalized therapy (Roche Cobas EGFR mutation test v2) (40). This assay can detect multiple mutations in exons 18, 19, 20 and 21 in NSCLC including L858R, T790M, G719X, S7681, and L861Q (41). Using ctDNA, 62.5% of patients were identified with EGFR mutations (exon 19 deletion, exon 20 T790 M insertion and exon 21 L858R mutation) at the baseline, while the rate of EGFR mutation positivity was higher among patients with metastatic disease (42).…”

Liquid Biopsy as a Prognostic and Theranostic Tool for the Management of Pancreatic Ductal Adenocarcinoma

“…With respect to ctDNA, there are a number of widely used applications in the identification and quantification technique of ctDNA. For example, identifying EGFR-tyrosine kinase (PTK) mutations from ctDNA for diagnostic purposes in patients with non-small cell lung cancer (NSCLC) (101,102). The identification of mutations in the EGFR-PTK pathways and testing potential therapeutics involving EGFR-PTK inhibitors and highlighting patients who are specifically sensitized or resistant to this treatment method.…”

Harnessing Liquid Biopsies to Guide Immune Checkpoint Inhibitor Therapy

“…However, ctDNA detectability varies from 0.01% to more than 90% of total cell free DNA (cfDNA), depending on tumor type, anatomical location, stage of the cancer, as well as the tumor microenvironment. Comparatively low ctDNA levels in patient blood samples with higher background cfDNA unrelated to tumor cells make detection a challenge [ 53 , 57 ]. Therefore, the standard procedure for blood collection and DNA isolation should be carefully selected and the detection technologies need to be extremely sensitive [ 29 , 54 ].…”