Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Purpose: Circulating cell-free DNA (cfDNA) level has been demonstrated to be associated with efficacy in first generation EGFR TKIs in non-small cell lung cancer (NSCLC). However, the role of dynamic cfDNA analysis using next-generation sequencing (NGS) in patients with subsequent third-generation EGFR TKIs remains unclear.
Methods: From 2016 to 2019, 81 NSCLC patients with T790M mutation either in tissue or plasma who received third-generation EGFR TKIs treatment were enrolled. CfDNA were sequenced by NGS with a 425-gene panel. The association of clinical characteristics, pretreatment, dynamic cfDNA and T790M level with outcomes in patients treated with the third-generation TKIs were analyzed.
Results: In univariate analysis, the median PFS of patients with undetectable cfDNA level during treatment was significantly longer than those with detectable cfDNA (16.97 . 6.10 months; HR 0.2109; < 0.0001). The median PFS of patients with undetectable T790M level during treatment was significantly longer than those with detectable T790M (14.1 . 4.4 months; HR 0.2192; < 0.001). Cox hazard proportion model showed that cfDNA clearance was an independent predictor for longer PFS (HR 0.3085; < 0.001) and longer OS (HR 0.499; = 0.034). The most common resistant mutations of the third-generation TKIs were C797S (24%). CNV, , D761N, Q791H, V843I, and mutation genes may possibly be new resistant mechanisms.
Conclusions: Patients with undetectable cfDNA during the third-generation EGFR TKI treatment have superior clinical outcomes, and dynamic cfDNA analysis by NGS is valuable to explore potential resistant mechanisms.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030263 | PMC |
| http://dx.doi.org/10.3389/fonc.2021.643199 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Intrinsically disordered region of Clr4/Suv39 regulates its enzymatic activity and ensures heterochromatin spreading.
Nucleic Acids Res
September 2025
Division of Chromatin Regulation, National Institute for Basic Biology, Okazaki 444-8585, Japan.
Methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin, is catalyzed by Clr4/Suv39. Clr4/Suv39 contains two conserved domains-an N-terminal chromodomain and a C-terminal catalytic domain-connected by an intrinsically disordered region (IDR). Several mechanisms have been proposed to regulate Clr4/Suv39 activity, but how it is regulated under physiological conditions remains largely unknown.
View Article and Find Full Text PDFClinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study.
ESMO Open
September 2025
Hospital del Mar Research Institute Barcelona, Medical Oncology Department, Hospital del Mar, Barcelona, Spain; Universitat Pompeu Fabra, Barcelona, Spain; Centro de Investigación Biomédica en Red de Oncología (CIBERONC-ISCIII), Madrid, Spain. Electronic address:
Background: Circulating tumor DNA (ctDNA) variations predict tumor response to systemic treatment (so-called molecular response) earlier than radiological assessment. However, a standardized categorization of molecular response is an unmet clinical need. Liquid biopsy-RECIST (LB-RECIST), based on aggregate variant allele frequency (aggVAF; sum of all detected variant allele frequencies in a sample) variations, has been proposed to stratify molecular response.
View Article and Find Full Text PDF4D-printed microdevices for spatiotemporal detection of ctDNA and miRNA in pancreatic cancer: an in-depth review.
Med Oncol
September 2025
Chemistry Department, Faculty of Science, Cairo University, Cairo, Egypt.
Pancreatic cancer is among the most lethal forms of cancer, with a five-year survival rate under 7%, primarily due to its late clinical presentation and rapid disease progression. Although the oncogenic development of pancreatic tumors can span over a decade, early diagnosis remains a major clinical challenge, as current diagnostic approaches-including imaging modalities and blood-based markers like CA19-9-lack the requisite sensitivity for detecting early-stage disease. Liquid biopsy has emerged as a promising, non-invasive diagnostic technique by enabling the detection of circulating tumor-specific nucleic acids, particularly circulating tumor DNA (ctDNA) and microRNAs (miRNAs).
View Article and Find Full Text PDFThe intracellular and extracellular fate of DNA and chromatin from micronuclei determines their pathogenicity.
Mutat Res Rev Mutat Res
September 2025
Natera Inc., Austin, TX, USA.
Circulating cell-free DNA (cfDNA), particularly in blood, is emerging as a critical non-invasive biomarker for the prediction, diagnosis, and monitoring of human diseases. Additionally, cytoplasmic DNA has been implicated in promoting genetic aberrations, genome instability, and inflammation-factors that can contribute to the development of various diseases, including cancer. However, the heterogeneous nature of both intra- and extracellular DNA presents a significant challenge.
View Article and Find Full Text PDFDevelopment and validation of a methylation-specific droplet digital PCR multiplex for lung cancer detection.
Sci Rep
September 2025
Department of Biochemistry and Immunology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark.
Biomarkers are increasingly used in cancer management, including lung cancer. The use of circulating tumour DNA (ctDNA) detection has attracted significant interest as a non-invasive, highly specific, and sensitive strategy. In this study, we developed and validated a methylation-specific droplet digital PCR (ddPCR) multiplex assay with five tumour-specific methylation markers identified by in silico analysis for lung cancer detection across various clinical settings.
View Article and Find Full Text PDF