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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1435537
This article is part of the Research Topic Unveiling the Potential of CTCs in Drug Resistance Mechanisms and Personalized Medicine View all 5 articles

Comprehensive Liquid Biopsy Analysis for Monitoring NSCLC Patients Under Second-line Osimertinib Treatment

Provisionally accepted
Aliki Ntzifa Aliki Ntzifa 1,2Theodoros Marras Theodoros Marras 2GALATEA KALLERGI GALATEA KALLERGI 3Athanasios Kotsakis Athanasios Kotsakis 4Vasilis Georgoulias Vasilis Georgoulias 5EVI LIANIDOU EVI LIANIDOU 2*
  • 1 National and Kapodistrian University of Athens, Athens, Greece
  • 2 Analysis of Circulating Tumor Cells Lab, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece
  • 3 Department of Biology, University of Patras, Patras, Greece
  • 4 Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece
  • 5 Metropolitan General Hospital, Holargos, Greece

The final, formatted version of the article will be published soon.

    The heterogeneous and complex genetic landscape of NSCLC impacts the clinical outcomes of patients who will eventually develop resistance to osimertinib. Liquid biopsy (LB) analysis as a minimally invasive approach is a key step to efficiently identify resistance mechanisms and adjust to proper subsequent treatments. In the present study, we combined plasma-cfDNA and CTC analysis from 30 NSCLC patients in samples collected before treatment and at the progression of disease (PD) and detected molecular alterations at the DNA mutation (EGFR, PIK3CA, KRAS G12C, BRAF V600E), DNA methylation (RASSF1A, BRMS1, FOXA1, SLFN1, SHISA3, RARĪ²,, WIF-1, RASSF10 and APC), gene expression (CK-19, CK-18, CK-8, AXL, TWIST-1, PD-L1, PIM-1, Vimentin, ALDH-1, and B2M ) and chromosomal level (HER2 and MET amplification) as possible resistance mechanisms and druggable targets. We studied the expression of PD-L1 in single CTCs using immunofluorescence. Our results reveal that comprehensive liquid biopsy analysis can efficiently represent the heterogeneous molecular landscape and provide prominent information on subsequent treatments for NSCLC patients at PD since druggable molecular alterations were detected in CTCs.

    Keywords: NSCLC, Osimertinib, liquid biopsy, CtDNA, CTC, Resistance

    Received: 20 May 2024; Accepted: 09 Sep 2024.

    Copyright: Ā© 2024 Ntzifa, Marras, KALLERGI, Kotsakis, Georgoulias and LIANIDOU. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: EVI LIANIDOU, Analysis of Circulating Tumor Cells Lab, Department of Chemistry, National and Kapodistrian University of Athens, Athens, Greece

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