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HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature

Introduction: Assessment of actionable gene mutations and oncogene fusions have made a paradigm shift in treatment strategies of non-small cell lung cancer (NSCLC). HRAS mutations involved around 0.2–0.8% of NSCLC patients, mostly on codon 61. For these patients, few data are available regarding cli...

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Autores principales: Mathiot, Laurent, Herbreteau, Guillaume, Robin, Siméon, Fenat, Charlotte, Bennouna, Jaafar, Blanquart, Christophe, Denis, Marc, Pons-Tostivint, Elvire
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139372/
https://www.ncbi.nlm.nih.gov/pubmed/35621690
http://dx.doi.org/10.3390/curroncol29050300
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author Mathiot, Laurent
Herbreteau, Guillaume
Robin, Siméon
Fenat, Charlotte
Bennouna, Jaafar
Blanquart, Christophe
Denis, Marc
Pons-Tostivint, Elvire
author_facet Mathiot, Laurent
Herbreteau, Guillaume
Robin, Siméon
Fenat, Charlotte
Bennouna, Jaafar
Blanquart, Christophe
Denis, Marc
Pons-Tostivint, Elvire
author_sort Mathiot, Laurent
collection PubMed
description Introduction: Assessment of actionable gene mutations and oncogene fusions have made a paradigm shift in treatment strategies of non-small cell lung cancer (NSCLC). HRAS mutations involved around 0.2–0.8% of NSCLC patients, mostly on codon 61. For these patients, few data are available regarding clinical characteristics and response to therapies. Methods: Next-Generation Sequencing (NGS) done routinely at Nantes University Hospital was used to identify HRAS molecular alterations in NSCLC patients. We identified and described four HRAS p.GlnQ61Leu mutated patients. Literature of previously HRAS-mutant NSCLC cases was reviewed, and available data in solid tumour with the most advanced H-Ras specific inhibitor, tipifarnib, were presented. Results: Of 1614 patients diagnosed with advanced NSCLC from January 2018 to December 2020, four (0.25%) had HRAS p.Gln61Leu mutation. Three of them died during the first-line systemic therapy. Furthermore, three additional cases were identified in literature. All cases were current or former smokers, most of them had pleural or pericardial effusion at diagnosis. Conclusions: The clinical course of patients with HRAS-mutant NSCLC remains unclear. Furthers cases should be identified in order to clarify prognosis and response to therapies. Tipifarnib, a farnesyl transferase inhibitor, is a promising candidate to target HRAS-mutant tumours and should be explored in NSCLC patients.
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spelling pubmed-91393722022-05-28 HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature Mathiot, Laurent Herbreteau, Guillaume Robin, Siméon Fenat, Charlotte Bennouna, Jaafar Blanquart, Christophe Denis, Marc Pons-Tostivint, Elvire Curr Oncol Case Report Introduction: Assessment of actionable gene mutations and oncogene fusions have made a paradigm shift in treatment strategies of non-small cell lung cancer (NSCLC). HRAS mutations involved around 0.2–0.8% of NSCLC patients, mostly on codon 61. For these patients, few data are available regarding clinical characteristics and response to therapies. Methods: Next-Generation Sequencing (NGS) done routinely at Nantes University Hospital was used to identify HRAS molecular alterations in NSCLC patients. We identified and described four HRAS p.GlnQ61Leu mutated patients. Literature of previously HRAS-mutant NSCLC cases was reviewed, and available data in solid tumour with the most advanced H-Ras specific inhibitor, tipifarnib, were presented. Results: Of 1614 patients diagnosed with advanced NSCLC from January 2018 to December 2020, four (0.25%) had HRAS p.Gln61Leu mutation. Three of them died during the first-line systemic therapy. Furthermore, three additional cases were identified in literature. All cases were current or former smokers, most of them had pleural or pericardial effusion at diagnosis. Conclusions: The clinical course of patients with HRAS-mutant NSCLC remains unclear. Furthers cases should be identified in order to clarify prognosis and response to therapies. Tipifarnib, a farnesyl transferase inhibitor, is a promising candidate to target HRAS-mutant tumours and should be explored in NSCLC patients. MDPI 2022-05-20 /pmc/articles/PMC9139372/ /pubmed/35621690 http://dx.doi.org/10.3390/curroncol29050300 Text en © 2022 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
Mathiot, Laurent
Herbreteau, Guillaume
Robin, Siméon
Fenat, Charlotte
Bennouna, Jaafar
Blanquart, Christophe
Denis, Marc
Pons-Tostivint, Elvire
HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature
title HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature
title_full HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature
title_fullStr HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature
title_full_unstemmed HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature
title_short HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature
title_sort hras q61l mutation as a possible target for non-small cell lung cancer: case series and review of literature
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139372/
https://www.ncbi.nlm.nih.gov/pubmed/35621690
http://dx.doi.org/10.3390/curroncol29050300
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