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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...

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Autores principales: Basse, Clémence, Trabelsi-Grati, Olfa, Masliah, Julien, Callens, Céline, Kamal, Maud, Freneaux, Paul, Klijanienko, Jerzy, Bieche, Ivan, Girard, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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