Targeting β-catenin in acute myeloid leukaemia: past, present, and future perspectives

Wagstaff, Megan, Coke, Brandon, Hodgkiss, Georgia R and Morgan, Rhys G (2022) Targeting β-catenin in acute myeloid leukaemia: past, present, and future perspectives. Bioscience Reports. ISSN 0144-8463

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Abstract

Acute myeloid leukaemia (AML) is an aggressive disease of the bone marrow with a poor prognosis. Evidence suggests long established chemotherapeutic regimens used to treat AML are reaching the limits of their efficacy, necessitating the urgent development of novel targeted therapies. Canonical Wnt signalling is an evolutionary conserved cascade heavily implicated in normal developmental and disease processes in humans. For over 15 years it's been known that the central mediator of this pathway, β-catenin, is dysregulated in AML promoting the emergence, maintenance, and drug resistance of leukaemia stem cells (LSC). Yet, despite this knowledge, and subsequent studies demonstrating the therapeutic potential of targeting Wnt activity in haematological cancers, β-catenin inhibitors have not yet reached the clinic. The aim of this review is to summarise the current understanding regarding the role and mechanistic dysregulation of β-catenin in AML and assess the therapeutic merit of pharmacologically targeting this molecule, drawing on lessons from other disease contexts.

Item Type: Article
Keywords: Wnt signalling, acute myeloid leukaemia, beta-catenin, small molecules
Schools and Departments: School of Life Sciences > Biochemistry
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 08 Apr 2022 07:38
Last Modified: 08 Apr 2022 07:45
URI: http://sro.sussex.ac.uk/id/eprint/105241

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