Molecular Pathways of Carcinogenesis in Familial Adenomatous Polyposis
Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by the presence of multiple polyps in the gastrointestinal tract and a wide range of systemic extra-intestinal manifestations. Patients affected will inevitably undergo abdominal surgery due to the malignant transformation of o...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5687 |
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| author | Ilaria Ditonno Domenico Novielli Francesca Celiberto Salvatore Rizzi Maria Rendina Enzo Ierardi Alfredo Di Leo Giuseppe Losurdo |
| author_facet | Ilaria Ditonno Domenico Novielli Francesca Celiberto Salvatore Rizzi Maria Rendina Enzo Ierardi Alfredo Di Leo Giuseppe Losurdo |
| author_sort | Ilaria Ditonno |
| collection | DOAJ |
| description | Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by the presence of multiple polyps in the gastrointestinal tract and a wide range of systemic extra-intestinal manifestations. Patients affected will inevitably undergo abdominal surgery due to the malignant transformation of one or more adenomas. The pathogenesis of the disease is based on a loss of function mutation in adenomatous polyposis coli (APC), a tumor-suppressor gene, inherited following a Mendelian pattern. This gene is a key component of multiple cell functions that cooperate for homeostasis; when mutated, it contributes to the progression of colorectal adenoma into cancer. Recent studies have demonstrated that several additional mechanisms may influence this process, such as alterations in gut microbiota composition and mucosal barrier immunity, interaction with the immune microenvironment and inflammation, the hormone estrogen, and other signaling pathways. These factors represent promising targets of future therapies and chemoprevention, aiming to alter the progressive nature of the disease and improve the quality of life of families affected. Therefore, we performed a narrative review about the current knowledge of the aforementioned pathways involved in colorectal cancer pathogenesis in FAP, exploring the genetic and environmental factors that may contribute to the development of CRC in FAP. |
| first_indexed | 2024-03-11T06:25:33Z |
| format | Article |
| id | doaj.art-ee465dab46274c8ca7ecc5bb35c8684c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:25:33Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ee465dab46274c8ca7ecc5bb35c8684c2023-11-17T11:37:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246568710.3390/ijms24065687Molecular Pathways of Carcinogenesis in Familial Adenomatous PolyposisIlaria Ditonno0Domenico Novielli1Francesca Celiberto2Salvatore Rizzi3Maria Rendina4Enzo Ierardi5Alfredo Di Leo6Giuseppe Losurdo7Section of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, ItalySection of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, ItalySection of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, ItalySection of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, ItalySection of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, ItalySection of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, ItalySection of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, ItalySection of Gastroenterology, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, ItalyFamilial adenomatous polyposis (FAP) is a genetic syndrome characterized by the presence of multiple polyps in the gastrointestinal tract and a wide range of systemic extra-intestinal manifestations. Patients affected will inevitably undergo abdominal surgery due to the malignant transformation of one or more adenomas. The pathogenesis of the disease is based on a loss of function mutation in adenomatous polyposis coli (APC), a tumor-suppressor gene, inherited following a Mendelian pattern. This gene is a key component of multiple cell functions that cooperate for homeostasis; when mutated, it contributes to the progression of colorectal adenoma into cancer. Recent studies have demonstrated that several additional mechanisms may influence this process, such as alterations in gut microbiota composition and mucosal barrier immunity, interaction with the immune microenvironment and inflammation, the hormone estrogen, and other signaling pathways. These factors represent promising targets of future therapies and chemoprevention, aiming to alter the progressive nature of the disease and improve the quality of life of families affected. Therefore, we performed a narrative review about the current knowledge of the aforementioned pathways involved in colorectal cancer pathogenesis in FAP, exploring the genetic and environmental factors that may contribute to the development of CRC in FAP.https://www.mdpi.com/1422-0067/24/6/5687familial adenomatous polyposisAPCcancerogenesismicrobiotaimmune microenvironmentestrogen |
| spellingShingle | Ilaria Ditonno Domenico Novielli Francesca Celiberto Salvatore Rizzi Maria Rendina Enzo Ierardi Alfredo Di Leo Giuseppe Losurdo Molecular Pathways of Carcinogenesis in Familial Adenomatous Polyposis International Journal of Molecular Sciences familial adenomatous polyposis APC cancerogenesis microbiota immune microenvironment estrogen |
| title | Molecular Pathways of Carcinogenesis in Familial Adenomatous Polyposis |
| title_full | Molecular Pathways of Carcinogenesis in Familial Adenomatous Polyposis |
| title_fullStr | Molecular Pathways of Carcinogenesis in Familial Adenomatous Polyposis |
| title_full_unstemmed | Molecular Pathways of Carcinogenesis in Familial Adenomatous Polyposis |
| title_short | Molecular Pathways of Carcinogenesis in Familial Adenomatous Polyposis |
| title_sort | molecular pathways of carcinogenesis in familial adenomatous polyposis |
| topic | familial adenomatous polyposis APC cancerogenesis microbiota immune microenvironment estrogen |
| url | https://www.mdpi.com/1422-0067/24/6/5687 |
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