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It has been more than 30 years since Nusse and Varmus identified a new mouse proto-oncogene int1 (integration 1), conserved across multiple species, and already recognised in Drosophila as Wingless (Wg). Wnts are now known to activate multiple signalling pathways, the best understood and extensively investigated being the canonical/β-catenin dependent pathway. β-catenin signalling has been found dysregulated to varying degrees and via multiple mechanisms in both solid and haematologic cancers, including multiple myeloma (MM). Recently developed inhibitors of the Wnt canonical pathway have proven to be potentially effective against MM, with minimal side effects. There is cautious optimism that some of these inhibitors will be added in our armamentarium against MM in the not so distant future. In this review, we discuss the possible mechanisms of Wnt-canonical pathway dysregulation in the pathogenesis of MM. Furthermore, we summarise the pathway inhibitors that have been validated in the disease in pre-clinical models or clinical trials and their potential challenges.
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