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AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a highly lethal malignancy that unfortunately cannot benefit from molecularly targeted therapies. Although previous results showed the pivotal role of various receptor tyrosine kinases (RTKs) in MPM tumorigenesis, the treatment with a single inhibitor targetin...

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Autores principales: Zito Marino, Federica, Della Corte, Carminia Maria, Ciaramella, Vincenza, Erra, Stefania, Ronchi, Andrea, Fiorelli, Alfonso, Vicidomini, Giovanni, Santini, Mario, Scognamiglio, Giosuè, Morgillo, Floriana, Ciardiello, Fortunato, Franco, Renato, Accardo, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783837/
https://www.ncbi.nlm.nih.gov/pubmed/36556214
http://dx.doi.org/10.3390/jpm12121993
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author Zito Marino, Federica
Della Corte, Carminia Maria
Ciaramella, Vincenza
Erra, Stefania
Ronchi, Andrea
Fiorelli, Alfonso
Vicidomini, Giovanni
Santini, Mario
Scognamiglio, Giosuè
Morgillo, Floriana
Ciardiello, Fortunato
Franco, Renato
Accardo, Marina
author_facet Zito Marino, Federica
Della Corte, Carminia Maria
Ciaramella, Vincenza
Erra, Stefania
Ronchi, Andrea
Fiorelli, Alfonso
Vicidomini, Giovanni
Santini, Mario
Scognamiglio, Giosuè
Morgillo, Floriana
Ciardiello, Fortunato
Franco, Renato
Accardo, Marina
author_sort Zito Marino, Federica
collection PubMed
description Malignant pleural mesothelioma (MPM) is a highly lethal malignancy that unfortunately cannot benefit from molecularly targeted therapies. Although previous results showed the pivotal role of various receptor tyrosine kinases (RTKs) in MPM tumorigenesis, the treatment with a single inhibitor targeting one specific RTK has been shown to be ineffective in MPM patients. The main aim of the present study was to investigate the potential role of AXL and MET receptors in MPM and the possible efficacy of treatment with AXL and MET multitarget inhibitors. Immunohistochemical and FISH analyses were performed in a wide series of formalin-fixed paraffin-embedded MPM samples to detect the expression of two receptors and the potential gene amplification. In vitro studies were performed to evaluate putative correlations between the target’s expression and the cell sensitivity to AXL-MET multitarget inhibitors. In our series, 10.4% of cases showed a co-expression of AXL and MET, regardless of their ligand expression, and the gene amplification. Furthermore, our in vitro results suggest that the concomitant pharmacological inhibition of AXL and MET may affect the proliferative and aggressiveness of MPM cells. In conclusion, the subset of MPM patients with AXL-MET co-activation could benefit from treatment with specific multitarget inhibitors.
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spelling pubmed-97838372022-12-24 AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma Zito Marino, Federica Della Corte, Carminia Maria Ciaramella, Vincenza Erra, Stefania Ronchi, Andrea Fiorelli, Alfonso Vicidomini, Giovanni Santini, Mario Scognamiglio, Giosuè Morgillo, Floriana Ciardiello, Fortunato Franco, Renato Accardo, Marina J Pers Med Article Malignant pleural mesothelioma (MPM) is a highly lethal malignancy that unfortunately cannot benefit from molecularly targeted therapies. Although previous results showed the pivotal role of various receptor tyrosine kinases (RTKs) in MPM tumorigenesis, the treatment with a single inhibitor targeting one specific RTK has been shown to be ineffective in MPM patients. The main aim of the present study was to investigate the potential role of AXL and MET receptors in MPM and the possible efficacy of treatment with AXL and MET multitarget inhibitors. Immunohistochemical and FISH analyses were performed in a wide series of formalin-fixed paraffin-embedded MPM samples to detect the expression of two receptors and the potential gene amplification. In vitro studies were performed to evaluate putative correlations between the target’s expression and the cell sensitivity to AXL-MET multitarget inhibitors. In our series, 10.4% of cases showed a co-expression of AXL and MET, regardless of their ligand expression, and the gene amplification. Furthermore, our in vitro results suggest that the concomitant pharmacological inhibition of AXL and MET may affect the proliferative and aggressiveness of MPM cells. In conclusion, the subset of MPM patients with AXL-MET co-activation could benefit from treatment with specific multitarget inhibitors. MDPI 2022-12-02 /pmc/articles/PMC9783837/ /pubmed/36556214 http://dx.doi.org/10.3390/jpm12121993 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 Article
Zito Marino, Federica
Della Corte, Carminia Maria
Ciaramella, Vincenza
Erra, Stefania
Ronchi, Andrea
Fiorelli, Alfonso
Vicidomini, Giovanni
Santini, Mario
Scognamiglio, Giosuè
Morgillo, Floriana
Ciardiello, Fortunato
Franco, Renato
Accardo, Marina
AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma
title AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma
title_full AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma
title_fullStr AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma
title_full_unstemmed AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma
title_short AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma
title_sort axl and met tyrosine kinase receptors co-expression as a potential therapeutic target in malignant pleural mesothelioma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783837/
https://www.ncbi.nlm.nih.gov/pubmed/36556214
http://dx.doi.org/10.3390/jpm12121993
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