Affiliation:
1. Biotech Research and Innovation Centre, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Abstract
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 RNF43 or RSPO 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 APC and CTNNB1, 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.
Funder
Danish Cancer Society
European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement
Danish Council for Independent Research
Novo Nordisk Foundation
Lundbeck Foundation
Cited by
4 articles.
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