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CFTR and Gastrointestinal Cancers: An Update

Cystic Fibrosis (CF) is a disease caused by mutations in the CFTR gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown to promote car...

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Autores principales: Bhattacharya, Rahul, Blankenheim, Zachary, Scott, Patricia M., Cormier, Robert T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224611/
https://www.ncbi.nlm.nih.gov/pubmed/35743652
http://dx.doi.org/10.3390/jpm12060868
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author Bhattacharya, Rahul
Blankenheim, Zachary
Scott, Patricia M.
Cormier, Robert T.
author_facet Bhattacharya, Rahul
Blankenheim, Zachary
Scott, Patricia M.
Cormier, Robert T.
author_sort Bhattacharya, Rahul
collection PubMed
description Cystic Fibrosis (CF) is a disease caused by mutations in the CFTR gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown to promote carcinogenesis. An example is the enhanced risk for several types of cancer in patients with CF, especially cancers of the GI tract. CFTR also acts as a tumor suppressor in diverse sporadic epithelial cancers in many tissues, primarily due to the silencing of CFTR expression via multiple mechanisms, but especially due to epigenetic regulation. This review provides an update on the latest research linking CFTR-deficiency to GI cancers, in both CF patients and in sporadic GI cancers, with a particular focus on cancer of the intestinal tract. It will discuss changes in the tissue landscape linked to CFTR-deficiency that may promote cancer development such as breakdowns in physical barriers, microbial dysbiosis and inflammation. It will also discuss molecular pathways and mechanisms that act upstream to modulate CFTR expression, such as by epigenetic silencing, as well as molecular pathways that act downstream of CFTR-deficiency, such as the dysregulation of the Wnt/β-catenin and NF-κB signaling pathways. Finally, it will discuss the emerging CFTR modulator drugs that have shown promising results in improving CFTR function in CF patients. The potential impact of these modulator drugs on the treatment and prevention of GI cancers can provide a new example of personalized cancer medicine.
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spelling pubmed-92246112022-06-24 CFTR and Gastrointestinal Cancers: An Update Bhattacharya, Rahul Blankenheim, Zachary Scott, Patricia M. Cormier, Robert T. J Pers Med Review Cystic Fibrosis (CF) is a disease caused by mutations in the CFTR gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown to promote carcinogenesis. An example is the enhanced risk for several types of cancer in patients with CF, especially cancers of the GI tract. CFTR also acts as a tumor suppressor in diverse sporadic epithelial cancers in many tissues, primarily due to the silencing of CFTR expression via multiple mechanisms, but especially due to epigenetic regulation. This review provides an update on the latest research linking CFTR-deficiency to GI cancers, in both CF patients and in sporadic GI cancers, with a particular focus on cancer of the intestinal tract. It will discuss changes in the tissue landscape linked to CFTR-deficiency that may promote cancer development such as breakdowns in physical barriers, microbial dysbiosis and inflammation. It will also discuss molecular pathways and mechanisms that act upstream to modulate CFTR expression, such as by epigenetic silencing, as well as molecular pathways that act downstream of CFTR-deficiency, such as the dysregulation of the Wnt/β-catenin and NF-κB signaling pathways. Finally, it will discuss the emerging CFTR modulator drugs that have shown promising results in improving CFTR function in CF patients. The potential impact of these modulator drugs on the treatment and prevention of GI cancers can provide a new example of personalized cancer medicine. MDPI 2022-05-25 /pmc/articles/PMC9224611/ /pubmed/35743652 http://dx.doi.org/10.3390/jpm12060868 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 Review
Bhattacharya, Rahul
Blankenheim, Zachary
Scott, Patricia M.
Cormier, Robert T.
CFTR and Gastrointestinal Cancers: An Update
title CFTR and Gastrointestinal Cancers: An Update
title_full CFTR and Gastrointestinal Cancers: An Update
title_fullStr CFTR and Gastrointestinal Cancers: An Update
title_full_unstemmed CFTR and Gastrointestinal Cancers: An Update
title_short CFTR and Gastrointestinal Cancers: An Update
title_sort cftr and gastrointestinal cancers: an update
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224611/
https://www.ncbi.nlm.nih.gov/pubmed/35743652
http://dx.doi.org/10.3390/jpm12060868
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