Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784857667977609216 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9783837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zitomarinofederica axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT dellacortecarminiamaria axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT ciaramellavincenza axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT errastefania axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT ronchiandrea axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT fiorellialfonso axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT vicidominigiovanni axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT santinimario axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT scognamigliogiosue axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT morgillofloriana axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT ciardiellofortunato axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT francorenato axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma AT accardomarina axlandmettyrosinekinasereceptorscoexpressionasapotentialtherapeutictargetinmalignantpleuralmesothelioma |