Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents
Primary liver cancers (PLCs) are steadily increasing in incidence and mortality in the world. They have a poor prognosis due to their silent nature, late discovery and resistance to common chemotherapy. At present, there are limited treatment alternatives, and the understanding of PLC molecular aspe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/8/1912 |
| _version_ | 1797436580656316416 |
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| author | Federico Selvaggi Teresa Catalano Roberto Cotellese Gitana Maria Aceto |
| author_facet | Federico Selvaggi Teresa Catalano Roberto Cotellese Gitana Maria Aceto |
| author_sort | Federico Selvaggi |
| collection | DOAJ |
| description | Primary liver cancers (PLCs) are steadily increasing in incidence and mortality in the world. They have a poor prognosis due to their silent nature, late discovery and resistance to common chemotherapy. At present, there are limited treatment alternatives, and the understanding of PLC molecular aspects is essential to develop more efficient drugs and therapeutic surgical and loco-regional strategies. A clear causal link with liver damage, inflammation, and regeneration has been found in the occurrence of PLC over the last few decades. Physiologically, Wingless/It (Wnt)-β-catenin signaling plays a key role in liver development, metabolic zonation and regeneration. Loss of functional homeostasis of this pathway appears to be a major driver of carcinogenesis in the liver parenchyma. In the hepatic microenvironment, molecular deregulations that exceed the Wnt signaling biological capacity can induce tumor initiation and progression. Indeed, somatic mutations are identified in key components of canonical and non-canonical Wnt signaling and in PLCs and precancerous lesions. In this review, the altered functions of Wnt/β-catenin signaling are considered in human PLCs, with emphasis on hepatocellular carcinomas (HCC), cholangiocarcinomas (CCA) and hepatoblastomas (HB). Based on recent literature, we also focused on liver cancerogenesis through Wnt deregulation. An overview of preclinical and clinical studies on approved and experimental drugs, targeting the Wnt/β-catenin cascade in PLCs, is proposed. In addition, the clinical implication of molecule inhibitors that have been shown to possess activity against the Wnt pathway in association with conventional surgical and loco-regional therapies are reviewed. |
| first_indexed | 2024-03-09T11:03:42Z |
| format | Article |
| id | doaj.art-f0ea14a8b3fe493f91598f48e3715e7c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T11:03:42Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f0ea14a8b3fe493f91598f48e3715e7c2023-12-01T01:05:35ZengMDPI AGCancers2072-66942022-04-01148191210.3390/cancers14081912Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic AgentsFederico Selvaggi0Teresa Catalano1Roberto Cotellese2Gitana Maria Aceto3Unit of General Surgery, Ospedale Floraspe Renzetti, 66034 Lanciano, Chieti, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, ItalyDepartment of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyDepartment of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, ItalyPrimary liver cancers (PLCs) are steadily increasing in incidence and mortality in the world. They have a poor prognosis due to their silent nature, late discovery and resistance to common chemotherapy. At present, there are limited treatment alternatives, and the understanding of PLC molecular aspects is essential to develop more efficient drugs and therapeutic surgical and loco-regional strategies. A clear causal link with liver damage, inflammation, and regeneration has been found in the occurrence of PLC over the last few decades. Physiologically, Wingless/It (Wnt)-β-catenin signaling plays a key role in liver development, metabolic zonation and regeneration. Loss of functional homeostasis of this pathway appears to be a major driver of carcinogenesis in the liver parenchyma. In the hepatic microenvironment, molecular deregulations that exceed the Wnt signaling biological capacity can induce tumor initiation and progression. Indeed, somatic mutations are identified in key components of canonical and non-canonical Wnt signaling and in PLCs and precancerous lesions. In this review, the altered functions of Wnt/β-catenin signaling are considered in human PLCs, with emphasis on hepatocellular carcinomas (HCC), cholangiocarcinomas (CCA) and hepatoblastomas (HB). Based on recent literature, we also focused on liver cancerogenesis through Wnt deregulation. An overview of preclinical and clinical studies on approved and experimental drugs, targeting the Wnt/β-catenin cascade in PLCs, is proposed. In addition, the clinical implication of molecule inhibitors that have been shown to possess activity against the Wnt pathway in association with conventional surgical and loco-regional therapies are reviewed.https://www.mdpi.com/2072-6694/14/8/1912liverWnt/β-catenin signalingmicroenvironmentHCCCCAHB |
| spellingShingle | Federico Selvaggi Teresa Catalano Roberto Cotellese Gitana Maria Aceto Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents Cancers liver Wnt/β-catenin signaling microenvironment HCC CCA HB |
| title | Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents |
| title_full | Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents |
| title_fullStr | Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents |
| title_full_unstemmed | Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents |
| title_short | Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents |
| title_sort | targeting wnt β catenin pathways in primary liver tumours from microenvironment signaling to therapeutic agents |
| topic | liver Wnt/β-catenin signaling microenvironment HCC CCA HB |
| url | https://www.mdpi.com/2072-6694/14/8/1912 |
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