Molecular Mechanisms and Therapies of Colorectal Cancer 2.0
Colorectal cancer (CRC) is currently the third leading cause of cancer-related mortality. Transforming growth factor beta (TGF-β) signaling has been associated with CRC growth and metastasis due to its involvement in proliferation, epithelial-to-mesenchymal transition (EMT), and angiogenesis. The TG...
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MDPI - Multidisciplinary Digital Publishing Institute
2024
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| Online adgang: | ONIX_20240514_9783725809516_544 |
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| description | Colorectal cancer (CRC) is currently the third leading cause of cancer-related mortality. Transforming growth factor beta (TGF-β) signaling has been associated with CRC growth and metastasis due to its involvement in proliferation, epithelial-to-mesenchymal transition (EMT), and angiogenesis. The TGF-β superfamily contains over forty members, including TGF-βs, Nodal, Activin, and bone morphogenetic proteins (BMPs). Three types of TGF-β receptors (TGFβRs) have been identified: types 1, 2, and 3. After ligand binding, TGF-βR2 recruits and phosphorylates TGF-βR1, which, in turn, phosphorylates downstream SMAD (small mother against decapentaplegic) proteins. Phosphorylated SMAD4 translocates into the nucleus, where it activates the transcription of numerous target genes (including SERPINE1, LTBP2, CDKN1A, ARID3B, ATXN1, PTPRK, RAB6A, SMAD7, EHBP1, etc.), acting predominantly as a tumor suppressor gene. Interestingly, alterations in SMAD4 are frequent in metastatic CRC and, together with TGF-βR2 gene mutations, have been reported as late events able to promote CRC progression. The study of the TGF-β pathway in metastatic CRC is challenging because of the great genetic heterogeneity of CRC. However, the increasing availability of targeted and whole-exome DNA sequencing techniques makes it possible to identify genetic mutations in complex, dynamic, and heterogeneous clinical contexts and make correlations with clinical outcomes. |
| format | Online |
| id | doab-20.500.12854ir-137929 |
| institution | Directory of Open Access Books |
| language | eng |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | MDPI - Multidisciplinary Digital Publishing Institute |
| publisherStr | MDPI - Multidisciplinary Digital Publishing Institute |
| record_format | ojs |
| spelling | doab-20.500.12854ir-1379292024-05-14T14:58:23Z Molecular Mechanisms and Therapies of Colorectal Cancer 2.0 Cave, Donatella Delle CD44 CD44v6 monoclonal antibody colorectal cancer exosome cancer exosomal miRNA lncRNA carcinogenesis colon cancer reactive oxygen species sleep fragmentation KRAS NRAS BRAF microsatellite instability HER2 colorectal cancer (CRC) muscarinic acetylcholine receptor M3 (M3R) expression human colorectal cancer survival tissue microarray immune cell markers TIA-1 therapeutic target synchronous metastatic colorectal cancer liquid biopsy PIK3CA anti-EGFR anti-VEGF ABCG2 prognosis survival protein–protein interaction network immunohistochemistry qPCR immune checkpoint inhibition nivolumab ipilimumab metastatic colorectal cancer FOXO pictilisib mucinous colorectal adenocarcinomas molecular mechanisms ATPase autophagy hepatocytes liver NAADP biomarkers bafilomycin A1 Ca2+ store n/a KRAS G12C colorectal cancer mechanism of resistance KRAS inhibitor pocket thema EDItEUR::M Medicine and Nursing::MB Medicine: general issues Colorectal cancer (CRC) is currently the third leading cause of cancer-related mortality. Transforming growth factor beta (TGF-β) signaling has been associated with CRC growth and metastasis due to its involvement in proliferation, epithelial-to-mesenchymal transition (EMT), and angiogenesis. The TGF-β superfamily contains over forty members, including TGF-βs, Nodal, Activin, and bone morphogenetic proteins (BMPs). Three types of TGF-β receptors (TGFβRs) have been identified: types 1, 2, and 3. After ligand binding, TGF-βR2 recruits and phosphorylates TGF-βR1, which, in turn, phosphorylates downstream SMAD (small mother against decapentaplegic) proteins. Phosphorylated SMAD4 translocates into the nucleus, where it activates the transcription of numerous target genes (including SERPINE1, LTBP2, CDKN1A, ARID3B, ATXN1, PTPRK, RAB6A, SMAD7, EHBP1, etc.), acting predominantly as a tumor suppressor gene. Interestingly, alterations in SMAD4 are frequent in metastatic CRC and, together with TGF-βR2 gene mutations, have been reported as late events able to promote CRC progression. The study of the TGF-β pathway in metastatic CRC is challenging because of the great genetic heterogeneity of CRC. However, the increasing availability of targeted and whole-exome DNA sequencing techniques makes it possible to identify genetic mutations in complex, dynamic, and heterogeneous clinical contexts and make correlations with clinical outcomes. 2024-05-14T14:58:20Z 2024-05-14T14:58:20Z 2024 book ONIX_20240514_9783725809516_544 9783725809516 9783725809523 https://directory.doabooks.org/handle/20.500.12854/137929 eng application/octet-stream Attribution-NonCommercial-NoDerivatives 4.0 International https://mdpi.com/books/pdfview/book/9194 https://mdpi.com/books/pdfview/book/9194 MDPI - Multidisciplinary Digital Publishing Institute 10.3390/books978-3-7258-0952-3 10.3390/books978-3-7258-0952-3 46cabcaa-dd94-4bfe-87b4-55023c1b36d0 9783725809516 9783725809523 186 open access |
| spellingShingle | CD44 CD44v6 monoclonal antibody colorectal cancer exosome cancer exosomal miRNA lncRNA carcinogenesis colon cancer reactive oxygen species sleep fragmentation KRAS NRAS BRAF microsatellite instability HER2 colorectal cancer (CRC) muscarinic acetylcholine receptor M3 (M3R) expression human colorectal cancer survival tissue microarray immune cell markers TIA-1 therapeutic target synchronous metastatic colorectal cancer liquid biopsy PIK3CA anti-EGFR anti-VEGF ABCG2 prognosis survival protein–protein interaction network immunohistochemistry qPCR immune checkpoint inhibition nivolumab ipilimumab metastatic colorectal cancer FOXO pictilisib mucinous colorectal adenocarcinomas molecular mechanisms ATPase autophagy hepatocytes liver NAADP biomarkers bafilomycin A1 Ca2+ store n/a KRAS G12C colorectal cancer mechanism of resistance KRAS inhibitor thema EDItEUR::M Medicine and Nursing::MB Medicine: general issues Molecular Mechanisms and Therapies of Colorectal Cancer 2.0 |
| title | Molecular Mechanisms and Therapies of Colorectal Cancer 2.0 |
| title_full | Molecular Mechanisms and Therapies of Colorectal Cancer 2.0 |
| title_fullStr | Molecular Mechanisms and Therapies of Colorectal Cancer 2.0 |
| title_full_unstemmed | Molecular Mechanisms and Therapies of Colorectal Cancer 2.0 |
| title_short | Molecular Mechanisms and Therapies of Colorectal Cancer 2.0 |
| title_sort | molecular mechanisms and therapies of colorectal cancer 2 0 |
| topic | CD44 CD44v6 monoclonal antibody colorectal cancer exosome cancer exosomal miRNA lncRNA carcinogenesis colon cancer reactive oxygen species sleep fragmentation KRAS NRAS BRAF microsatellite instability HER2 colorectal cancer (CRC) muscarinic acetylcholine receptor M3 (M3R) expression human colorectal cancer survival tissue microarray immune cell markers TIA-1 therapeutic target synchronous metastatic colorectal cancer liquid biopsy PIK3CA anti-EGFR anti-VEGF ABCG2 prognosis survival protein–protein interaction network immunohistochemistry qPCR immune checkpoint inhibition nivolumab ipilimumab metastatic colorectal cancer FOXO pictilisib mucinous colorectal adenocarcinomas molecular mechanisms ATPase autophagy hepatocytes liver NAADP biomarkers bafilomycin A1 Ca2+ store n/a KRAS G12C colorectal cancer mechanism of resistance KRAS inhibitor thema EDItEUR::M Medicine and Nursing::MB Medicine: general issues |
| topic_facet | CD44 CD44v6 monoclonal antibody colorectal cancer exosome cancer exosomal miRNA lncRNA carcinogenesis colon cancer reactive oxygen species sleep fragmentation KRAS NRAS BRAF microsatellite instability HER2 colorectal cancer (CRC) muscarinic acetylcholine receptor M3 (M3R) expression human colorectal cancer survival tissue microarray immune cell markers TIA-1 therapeutic target synchronous metastatic colorectal cancer liquid biopsy PIK3CA anti-EGFR anti-VEGF ABCG2 prognosis survival protein–protein interaction network immunohistochemistry qPCR immune checkpoint inhibition nivolumab ipilimumab metastatic colorectal cancer FOXO pictilisib mucinous colorectal adenocarcinomas molecular mechanisms ATPase autophagy hepatocytes liver NAADP biomarkers bafilomycin A1 Ca2+ store n/a KRAS G12C colorectal cancer mechanism of resistance KRAS inhibitor thema EDItEUR::M Medicine and Nursing::MB Medicine: general issues |
| url | ONIX_20240514_9783725809516_544 |