The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options
It is well established that mutations in the canonical WNT-signalling pathway play a major role in various cancers. Critical to developing new therapeutic strategies is understanding which cancers are driven by WNT pathway activation and at what level these mutations occur within the pathway. Some c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/7/990 |
| _version_ | 1797608213747597312 |
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| author | Wibke Groenewald Anders H. Lund David Michael Gay |
| author_facet | Wibke Groenewald Anders H. Lund David Michael Gay |
| author_sort | Wibke Groenewald |
| collection | DOAJ |
| description | It is well established that mutations in the canonical WNT-signalling pathway play a major role in various cancers. Critical to developing new therapeutic strategies is understanding which cancers are driven by WNT pathway activation and at what level these mutations occur within the pathway. Some cancers harbour mutations in genes whose protein products operate at the receptor level of the WNT pathway. For instance, tumours with <i>RNF43</i> or <i>RSPO</i> mutations, still require exogenous WNT ligands to drive WNT signalling (ligand-dependent mutations). Conversely, mutations within the cytoplasmic segment of the Wnt pathway, such as in <i>APC</i> and <i>CTNNB1</i>, lead to constitutive WNT pathway activation even in the absence of WNT ligands (ligand-independent). Here, we review the predominant driving mutations found in cancer that lead to WNT pathway activation, as well as explore some of the therapeutic interventions currently available against tumours harbouring either ligand-dependent or ligand-independent mutations. Finally, we discuss a potentially new therapeutic avenue by targeting the translational apparatus downstream from WNT signalling. |
| first_indexed | 2024-03-11T05:41:22Z |
| format | Article |
| id | doaj.art-dd978339ad6840da8e56975c0c3f4072 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:41:22Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-dd978339ad6840da8e56975c0c3f40722023-11-17T16:27:43ZengMDPI AGCells2073-44092023-03-0112799010.3390/cells12070990The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic OptionsWibke Groenewald0Anders H. Lund1David Michael Gay2Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkBiotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkBiotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkIt is well established that mutations in the canonical WNT-signalling pathway play a major role in various cancers. Critical to developing new therapeutic strategies is understanding which cancers are driven by WNT pathway activation and at what level these mutations occur within the pathway. Some cancers harbour mutations in genes whose protein products operate at the receptor level of the WNT pathway. For instance, tumours with <i>RNF43</i> or <i>RSPO</i> mutations, still require exogenous WNT ligands to drive WNT signalling (ligand-dependent mutations). Conversely, mutations within the cytoplasmic segment of the Wnt pathway, such as in <i>APC</i> and <i>CTNNB1</i>, lead to constitutive WNT pathway activation even in the absence of WNT ligands (ligand-independent). Here, we review the predominant driving mutations found in cancer that lead to WNT pathway activation, as well as explore some of the therapeutic interventions currently available against tumours harbouring either ligand-dependent or ligand-independent mutations. Finally, we discuss a potentially new therapeutic avenue by targeting the translational apparatus downstream from WNT signalling.https://www.mdpi.com/2073-4409/12/7/990WNTAPCβ-cateninligand-dependentcolon cancerendometrial cancer |
| spellingShingle | Wibke Groenewald Anders H. Lund David Michael Gay The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options Cells WNT APC β-catenin ligand-dependent colon cancer endometrial cancer |
| title | The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options |
| title_full | The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options |
| title_fullStr | The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options |
| title_full_unstemmed | The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options |
| title_short | The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options |
| title_sort | role of wnt pathway mutations in cancer development and an overview of therapeutic options |
| topic | WNT APC β-catenin ligand-dependent colon cancer endometrial cancer |
| url | https://www.mdpi.com/2073-4409/12/7/990 |
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