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Gain of Aggressive Histological and Molecular Patterns after Acquired Resistance to Novel Anti-EGFR Therapies in Non-Small Cell Lung Cancer
Novel anti-EGFR therapies target resistance to standard-of-care anti-EGFR in patients with metastatic lung cancer. We describe tumors at progression versus at the initiation of novel anti-EGFR agents in patients with metastatic lung adenocarcinoma harboring EGFR mutation. This clinical case series r...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965794/ https://www.ncbi.nlm.nih.gov/pubmed/36835213 http://dx.doi.org/10.3390/ijms24043802 |
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author | Basse, Clémence Trabelsi-Grati, Olfa Masliah, Julien Callens, Céline Kamal, Maud Freneaux, Paul Klijanienko, Jerzy Bieche, Ivan Girard, Nicolas |
author_facet | Basse, Clémence Trabelsi-Grati, Olfa Masliah, Julien Callens, Céline Kamal, Maud Freneaux, Paul Klijanienko, Jerzy Bieche, Ivan Girard, Nicolas |
author_sort | Basse, Clémence |
collection | PubMed |
description | Novel anti-EGFR therapies target resistance to standard-of-care anti-EGFR in patients with metastatic lung cancer. We describe tumors at progression versus at the initiation of novel anti-EGFR agents in patients with metastatic lung adenocarcinoma harboring EGFR mutation. This clinical case series reports the histological and genomic features and their evolution following disease progression under amivantamab or patritumab-deruxtecan in clinical trials. All patients had a biopsy at disease progression. Four patients harboring EGFR gene mutations were included. Three of them received anterior anti-EGFR treatment. Median delay to disease progression was 15 months (range: 4–24). At progression, all tumors presented a mutation in the TP53 signaling pathway associated with a loss of heterozygosis (LOH) of the allele in 75% (n = 3), and two tumors (50%) presented an RB1 mutation associated with LOH. Ki67 expression increased above 50% (range 50–90%) in all samples compared to baseline (range 10–30%), and one tumor expressed a positive neuroendocrine marker at progression. Our work reports the potential molecular mechanisms of resistance under novel anti-EGFR in patients with metastatic EGFR-mutated lung adenocarcinoma, with the transformation to a more aggressive histology with acquired TP53 mutation and/or the increase in Ki67 expression. These characteristics are usually found in aggressive Small Cell Lung Cancer. |
format | Online Article Text |
id | pubmed-9965794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99657942023-02-26 Gain of Aggressive Histological and Molecular Patterns after Acquired Resistance to Novel Anti-EGFR Therapies in Non-Small Cell Lung Cancer Basse, Clémence Trabelsi-Grati, Olfa Masliah, Julien Callens, Céline Kamal, Maud Freneaux, Paul Klijanienko, Jerzy Bieche, Ivan Girard, Nicolas Int J Mol Sci Case Report Novel anti-EGFR therapies target resistance to standard-of-care anti-EGFR in patients with metastatic lung cancer. We describe tumors at progression versus at the initiation of novel anti-EGFR agents in patients with metastatic lung adenocarcinoma harboring EGFR mutation. This clinical case series reports the histological and genomic features and their evolution following disease progression under amivantamab or patritumab-deruxtecan in clinical trials. All patients had a biopsy at disease progression. Four patients harboring EGFR gene mutations were included. Three of them received anterior anti-EGFR treatment. Median delay to disease progression was 15 months (range: 4–24). At progression, all tumors presented a mutation in the TP53 signaling pathway associated with a loss of heterozygosis (LOH) of the allele in 75% (n = 3), and two tumors (50%) presented an RB1 mutation associated with LOH. Ki67 expression increased above 50% (range 50–90%) in all samples compared to baseline (range 10–30%), and one tumor expressed a positive neuroendocrine marker at progression. Our work reports the potential molecular mechanisms of resistance under novel anti-EGFR in patients with metastatic EGFR-mutated lung adenocarcinoma, with the transformation to a more aggressive histology with acquired TP53 mutation and/or the increase in Ki67 expression. These characteristics are usually found in aggressive Small Cell Lung Cancer. MDPI 2023-02-14 /pmc/articles/PMC9965794/ /pubmed/36835213 http://dx.doi.org/10.3390/ijms24043802 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Case Report Basse, Clémence Trabelsi-Grati, Olfa Masliah, Julien Callens, Céline Kamal, Maud Freneaux, Paul Klijanienko, Jerzy Bieche, Ivan Girard, Nicolas Gain of Aggressive Histological and Molecular Patterns after Acquired Resistance to Novel Anti-EGFR Therapies in Non-Small Cell Lung Cancer |
title | Gain of Aggressive Histological and Molecular Patterns after Acquired Resistance to Novel Anti-EGFR Therapies in Non-Small Cell Lung Cancer |
title_full | Gain of Aggressive Histological and Molecular Patterns after Acquired Resistance to Novel Anti-EGFR Therapies in Non-Small Cell Lung Cancer |
title_fullStr | Gain of Aggressive Histological and Molecular Patterns after Acquired Resistance to Novel Anti-EGFR Therapies in Non-Small Cell Lung Cancer |
title_full_unstemmed | Gain of Aggressive Histological and Molecular Patterns after Acquired Resistance to Novel Anti-EGFR Therapies in Non-Small Cell Lung Cancer |
title_short | Gain of Aggressive Histological and Molecular Patterns after Acquired Resistance to Novel Anti-EGFR Therapies in Non-Small Cell Lung Cancer |
title_sort | gain of aggressive histological and molecular patterns after acquired resistance to novel anti-egfr therapies in non-small cell lung cancer |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965794/ https://www.ncbi.nlm.nih.gov/pubmed/36835213 http://dx.doi.org/10.3390/ijms24043802 |
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