WNT signalling pathways as therapeutic targets in cancer

@article{Anastas2012WNTSP,
  title={WNT signalling pathways as therapeutic targets in cancer},
  author={Jamie N. Anastas and Randall T. Moon},
  journal={Nature Reviews Cancer},
  year={2012},
  volume={13},
  pages={11-26}
}
Since the initial discovery of the oncogenic activity of WNT1 in mouse mammary glands, our appreciation for the complex roles for WNT signalling pathways in cancer has increased dramatically. WNTs and their downstream effectors regulate various processes that are important for cancer progression, including tumour initiation, tumour growth, cell senescence, cell death, differentiation and metastasis. Although WNT signalling pathways have been difficult to target, improved drug-discovery… 
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The evidence supporting the WNT pathway in cancer, the therapeutic strategies in modulating this pathway, and potential challenges in drug development are evaluated.
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Current evidence for the cancer‐promoting activity of Dickkopf‐1 and recent insights into the effects of DKK1 on signalling pathways in both cancer and immune cells are reviewed.
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Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression.
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The small-molecule inhibitors targeting various components of Wnt signaling pathways are reviewed and the progress from the discovery of lead compounds to highly potent inhibitors with significant therapeutic potential is reviewed.
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Issues regarding the roles of both canonical and non-canonical Wnt signaling pathways in cancer will be explored, mainly concerning their role in the maintenance of cancer stemness, in the metabolism reprograming of cancer cells and in the modulation of the tumor microenvironment.
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It is concluded that therapies targeting the Wnt pathway may play an essential role in the future of anticancer therapeutics, both alone or in conjunction with traditional therapies.
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The potential therapeutic agents that have been developed to date for inhibition of the Wnt/β-catenin cascade are reviewed as well as current status of clinical trials of some of these agents.
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The experimental evidence supporting oncogenic roles of WNT signaling in GBM is summarized, the discovery of agents that can inhibit W NT signaling in preclinical models and the current status of human clinical trials are discussed.
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Current insights into novel components of Wnt pathways are reviewed and how Wnt signaling affects maintenance of cancer stem cells, metastasis and immune control are described.
WNT Signaling: an Emerging Mediator of Cancer Cell Metabolism?
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A review highlights the emerging evidence for WNT signaling in the reprogramming of cancer cell metabolism and examines the role of these signaling pathways as mediators of tumor bioenergetics.
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