WNT signalling pathways as therapeutic targets in cancer

  title={WNT signalling pathways as therapeutic targets in cancer},
  author={Jamie N. Anastas and Randall T. Moon},
  journal={Nature Reviews Cancer},
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… 
Targeting the WNT Signaling Pathway in Cancer Therapeutics.
The evidence supporting the WNT pathway in cancer, the therapeutic strategies in modulating this pathway, and potential challenges in drug development are evaluated.
Rationale for targeting the Wnt signalling modulator Dickkopf‐1 for oncology
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.
WNT signalling in prostate cancer
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.
Small-molecule inhibitors of Wnt signaling pathway: towards novel anticancer therapeutics.
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.
Wnt Signaling: Paths for Cancer Progression.
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.
The role of Wnt signaling pathway in carcinogenesis and implications for anticancer therapeutics
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.
Development of anticancer agents targeting the Wnt/β-catenin signaling.
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.
WNT signaling in glioblastoma and therapeutic opportunities
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.
Wnt signaling in cancer
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?
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.


The links between axin and carcinogenesis
This review explores the intriguing connections between defects in axin function and human diseases and indicates that these molecules are the primary limiting components of this pathway.
Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer
Two novel classes of small molecules are discovered that disrupt Wnt pathway responses and contribute to Wnt-independent signal transduction pathways and thus could be broadly exploited for chemical genetics and therapeutic goals.
Epigenetic gene silencing in the Wnt pathway in breast cancer
It appears that DNA hypermethylation leads to aberrant regulation of the Wnt pathway in breast cancer, and as such, this review focuses on the epigenetic regulation of Wnt pathways components in breast cancers.
A Wnt–Axin2–GSK3β cascade regulates Snail1 activity in breast cancer cells
It is demonstrated that canonical Wnt signalling engages tumour cell dedifferentiation and tissue-invasive activity through an Axin2-dependent pathway that stabilizes the Snail1 zinc-transcription factor, a key regulator of normal and neoplastic EMT programmes.
Proximal events in Wnt signal transduction
Intriguingly, the transmembrane receptor Tyr kinases Ror2 and Ryk, as well as Frizzled receptors that act independently of LRP5 or LRP6, function as receptors for Wnt and activate β-catenin-independent pathways, which leads to changes in cell movement and polarity and to the antagonism of the β- catenin pathway.
Wnt/Fz signaling and the cytoskeleton: potential roles in tumorigenesis
The possible roles of both β-catenin-dependent and -independent signaling pathways in tumor progression are discussed, with an emphasis on their regulation of Rho-family GTPases, cytoskeletal remodeling, and relationships with cell-cell adhesion and cilia/ciliogenesis.
Inhibition of Wnt signaling by Dishevelled PDZ peptides.
It is found that the binding cleft of the Dishevelled PDZ domain is more flexible than those of canonical PDZ domains and enables recognition of both C-terminal and internal peptides.
Inhibition of Wnt signaling downregulates Akt activity and induces chemosensitivity in PTEN‐mutated prostate cancer cells
It is found that WIF‐1 downregulates the Akt pathway and also enhances chemosensitivity in PTEN‐null Pca cells.
Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines.
  • T. Pukrop, F. Klemm, C. Binder
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2006
It is demonstrated that coculture of MCF-7 cells and macrophages leads to up-regulation of Wnt 5a in the latter, which is essential for macrophage-induced invasiveness.