CFTR and Gastrointestinal Cancers: An Update
Cystic Fibrosis (CF) is a disease caused by mutations in the <i>CFTR</i> 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 s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/6/868 |
| _version_ | 1797485541973819392 |
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| author | Rahul Bhattacharya Zachary Blankenheim Patricia M. Scott Robert T. Cormier |
| author_facet | Rahul Bhattacharya Zachary Blankenheim Patricia M. Scott Robert T. Cormier |
| author_sort | Rahul Bhattacharya |
| collection | DOAJ |
| description | Cystic Fibrosis (CF) is a disease caused by mutations in the <i>CFTR</i> 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. |
| first_indexed | 2024-03-09T23:21:15Z |
| format | Article |
| id | doaj.art-3651b7a663fe4a9788ae6d73049f2ea7 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T23:21:15Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-3651b7a663fe4a9788ae6d73049f2ea72023-11-23T17:26:46ZengMDPI AGJournal of Personalized Medicine2075-44262022-05-0112686810.3390/jpm12060868CFTR and Gastrointestinal Cancers: An UpdateRahul Bhattacharya0Zachary Blankenheim1Patricia M. Scott2Robert T. Cormier3Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55812, USADepartment of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55812, USADepartment of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55812, USADepartment of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55812, USACystic Fibrosis (CF) is a disease caused by mutations in the <i>CFTR</i> 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.https://www.mdpi.com/2075-4426/12/6/868cystic fibrosisCFTRgastrointestinal cancerstumor suppressor genemodulators |
| spellingShingle | Rahul Bhattacharya Zachary Blankenheim Patricia M. Scott Robert T. Cormier CFTR and Gastrointestinal Cancers: An Update Journal of Personalized Medicine cystic fibrosis CFTR gastrointestinal cancers tumor suppressor gene modulators |
| 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 | cystic fibrosis CFTR gastrointestinal cancers tumor suppressor gene modulators |
| url | https://www.mdpi.com/2075-4426/12/6/868 |
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