Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy

Abstract Nonsense-mediated mRNA decay (NMD) is a highly conserved cellular surveillance mechanism, commonly studied for its role in mRNA quality control because of its capacity of degrading mutated mRNAs that would produce truncated proteins. However, recent studies have proven that NMD hides more c...

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Autores principales:	Roberta Bongiorno, Mario Paolo Colombo, Daniele Lecis
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Neoantigens Immune checkpoint inhibitors Nonsense mutations Combination therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/99e0e643f82840e9937f59e512b30aa1
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spelling	oai:doaj.org-article:99e0e643f82840e9937f59e512b30aa12021-12-05T12:10:12ZDeciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy10.1186/s13046-021-02192-21756-9966https://doaj.org/article/99e0e643f82840e9937f59e512b30aa12021-12-01T00:00:00Zhttps://doi.org/10.1186/s13046-021-02192-2https://doaj.org/toc/1756-9966Abstract Nonsense-mediated mRNA decay (NMD) is a highly conserved cellular surveillance mechanism, commonly studied for its role in mRNA quality control because of its capacity of degrading mutated mRNAs that would produce truncated proteins. However, recent studies have proven that NMD hides more complex tasks involved in a plethora of cellular activities. Indeed, it can control the stability of mutated as well as non-mutated transcripts, tuning transcriptome regulation. NMD not only displays a pivotal role in cell physiology but also in a number of genetic diseases. In cancer, the activity of this pathway is extremely complex and it is endowed with both pro-tumor and tumor suppressor functions, likely depending on the genetic context and tumor microenvironment. NMD inhibition has been tested in pre-clinical studies showing favored production of neoantigens by cancer cells, which can stimulate the triggering of an anti-tumor immune response. At the same time, NMD inhibition could result in a pro-tumor effect, increasing cancer cell adaptation to stress. Since several NMD inhibitors are already available in the clinic to treat genetic diseases, these compounds could be redirected to treat cancer patients, pending the comprehension of these variegated NMD regulation mechanisms. Ideally, an effective strategy should exploit the anti-tumor advantages of NMD inhibition and simultaneously preserve its intrinsic tumor suppressor functions. The targeting of NMD could provide a new therapeutic opportunity, increasing the immunogenicity of tumors and potentially boosting the efficacy of the immunotherapy agents now available for cancer treatment.Roberta BongiornoMario Paolo ColomboDaniele LecisBMCarticleNeoantigensImmune checkpoint inhibitorsNonsense mutationsCombination therapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoantigens Immune checkpoint inhibitors Nonsense mutations Combination therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoantigens Immune checkpoint inhibitors Nonsense mutations Combination therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Roberta Bongiorno Mario Paolo Colombo Daniele Lecis Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy
description	Abstract Nonsense-mediated mRNA decay (NMD) is a highly conserved cellular surveillance mechanism, commonly studied for its role in mRNA quality control because of its capacity of degrading mutated mRNAs that would produce truncated proteins. However, recent studies have proven that NMD hides more complex tasks involved in a plethora of cellular activities. Indeed, it can control the stability of mutated as well as non-mutated transcripts, tuning transcriptome regulation. NMD not only displays a pivotal role in cell physiology but also in a number of genetic diseases. In cancer, the activity of this pathway is extremely complex and it is endowed with both pro-tumor and tumor suppressor functions, likely depending on the genetic context and tumor microenvironment. NMD inhibition has been tested in pre-clinical studies showing favored production of neoantigens by cancer cells, which can stimulate the triggering of an anti-tumor immune response. At the same time, NMD inhibition could result in a pro-tumor effect, increasing cancer cell adaptation to stress. Since several NMD inhibitors are already available in the clinic to treat genetic diseases, these compounds could be redirected to treat cancer patients, pending the comprehension of these variegated NMD regulation mechanisms. Ideally, an effective strategy should exploit the anti-tumor advantages of NMD inhibition and simultaneously preserve its intrinsic tumor suppressor functions. The targeting of NMD could provide a new therapeutic opportunity, increasing the immunogenicity of tumors and potentially boosting the efficacy of the immunotherapy agents now available for cancer treatment.
format	article
author	Roberta Bongiorno Mario Paolo Colombo Daniele Lecis
author_facet	Roberta Bongiorno Mario Paolo Colombo Daniele Lecis
author_sort	Roberta Bongiorno
title	Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy
title_short	Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy
title_full	Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy
title_fullStr	Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy
title_full_unstemmed	Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy
title_sort	deciphering the nonsense-mediated mrna decay pathway to identify cancer cell vulnerabilities for effective cancer therapy
publisher	BMC
publishDate	2021
url	https://doaj.org/article/99e0e643f82840e9937f59e512b30aa1
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Deciphering the nonsense-mediated mRNA decay pathway to identify cancer cell vulnerabilities for effective cancer therapy

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