Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer

Abstract Despite advances in its treatment, lung cancer still represents the most common and lethal tumor. Because of that, efforts to decipher the pathophysiological actors that may promote lung tumor generation/progression are being made, with the final aim of establishing new therapeutic options....

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Autores principales:	Adrián Sánchez-Fdez, María Florencia Re-Louhau, Pablo Rodríguez-Núñez, Dolores Ludeña, Sofía Matilla-Almazán, Atanasio Pandiella, Azucena Esparís-Ogando
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/86e191c9001f42a08729239785058682
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spelling	oai:doaj.org-article:86e191c9001f42a087292397850586822021-12-02T15:10:33ZClinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer10.1038/s41698-021-00218-82397-768Xhttps://doaj.org/article/86e191c9001f42a087292397850586822021-08-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00218-8https://doaj.org/toc/2397-768XAbstract Despite advances in its treatment, lung cancer still represents the most common and lethal tumor. Because of that, efforts to decipher the pathophysiological actors that may promote lung tumor generation/progression are being made, with the final aim of establishing new therapeutic options. Using a transgenic mouse model, we formerly demonstrated that the sole activation of the MEK5/ERK5 MAPK route had a pathophysiological role in the onset of lung adenocarcinomas. Given the prevalence of that disease and its frequent dismal prognosis, our findings opened the possibility of targeting the MEK5/ERK5 route with therapeutic purposes. Here we have explored such possibility. We found that increased levels of MEK5/ERK5 correlated with poor patient prognosis in lung cancer. Moreover, using genetic as well as pharmacological tools, we show that targeting the MEK5/ERK5 route is therapeutically effective in lung cancer. Not only genetic disruption of ERK5 by CRISPR/Cas9 caused a relevant inhibition of tumor growth in vitro and in vivo; such ERK5 deficit augmented the antitumoral effect of agents normally used in the lung cancer clinic. The clinical correlation studies together with the pharmacological and genetic results establish the basis for considering the targeting of the MEK5/ERK5 route in the therapy for lung cancer.Adrián Sánchez-FdezMaría Florencia Re-LouhauPablo Rodríguez-NúñezDolores LudeñaSofía Matilla-AlmazánAtanasio PandiellaAzucena Esparís-OgandoNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Adrián Sánchez-Fdez María Florencia Re-Louhau Pablo Rodríguez-Núñez Dolores Ludeña Sofía Matilla-Almazán Atanasio Pandiella Azucena Esparís-Ogando Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer
description	Abstract Despite advances in its treatment, lung cancer still represents the most common and lethal tumor. Because of that, efforts to decipher the pathophysiological actors that may promote lung tumor generation/progression are being made, with the final aim of establishing new therapeutic options. Using a transgenic mouse model, we formerly demonstrated that the sole activation of the MEK5/ERK5 MAPK route had a pathophysiological role in the onset of lung adenocarcinomas. Given the prevalence of that disease and its frequent dismal prognosis, our findings opened the possibility of targeting the MEK5/ERK5 route with therapeutic purposes. Here we have explored such possibility. We found that increased levels of MEK5/ERK5 correlated with poor patient prognosis in lung cancer. Moreover, using genetic as well as pharmacological tools, we show that targeting the MEK5/ERK5 route is therapeutically effective in lung cancer. Not only genetic disruption of ERK5 by CRISPR/Cas9 caused a relevant inhibition of tumor growth in vitro and in vivo; such ERK5 deficit augmented the antitumoral effect of agents normally used in the lung cancer clinic. The clinical correlation studies together with the pharmacological and genetic results establish the basis for considering the targeting of the MEK5/ERK5 route in the therapy for lung cancer.
format	article
author	Adrián Sánchez-Fdez María Florencia Re-Louhau Pablo Rodríguez-Núñez Dolores Ludeña Sofía Matilla-Almazán Atanasio Pandiella Azucena Esparís-Ogando
author_facet	Adrián Sánchez-Fdez María Florencia Re-Louhau Pablo Rodríguez-Núñez Dolores Ludeña Sofía Matilla-Almazán Atanasio Pandiella Azucena Esparís-Ogando
author_sort	Adrián Sánchez-Fdez
title	Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer
title_short	Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer
title_full	Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer
title_fullStr	Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer
title_full_unstemmed	Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer
title_sort	clinical, genetic and pharmacological data support targeting the mek5/erk5 module in lung cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/86e191c9001f42a08729239785058682
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Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer

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