Wnt pathway modulators in cancer therapeutics: An update on completed and ongoing clinical trials

Neiheisel, Ann; Kaur, Manpreet; Ma, Nancy; Havard, Patty; Shenoy, Anitha

doi:10.1002/ijc.33811

Cited by 62 publications

(35 citation statements)

References 103 publications

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“…Especially, canonical Wnt/β-catenin signaling is often hyperactivated in cancers and has a significant role in the occurrence and progression of the disease [ 1 , 2 , 97 , 98 ]. The clinical implications of potent drugs targeting this signaling to inhibit different tumors have been assessed [ 99 – 101 ], and the current pharmacological intervention mainly focuses on inhibiting Wnt molecules and their receptors, stabilizing the “destruction protein complex” of β-catenin, blocking the activity of β-catenin, as well as suppressing the interaction of β-catenin with its co-factors [ 100 , 101 ]. However, the molecular mechanism related to the modulation of Wnt/β-catenin signaling in different types of tumor is complicated.…”

Section: Discussionmentioning

confidence: 99%

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

You

Kong

et al. 2022

Cell Mol Biol Lett

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Canonical Wnt/β-catenin signaling is a complex cell-communication mechanism that has a central role in the progression of various cancers. The cellular factors that participate in the regulation of this signaling are still not fully elucidated. Lysine acetylation is a significant protein modification which facilitates reversible regulation of the target protein function dependent on the activity of lysine acetyltransferases (KATs) and the catalytic function of lysine deacetylases (KDACs). Protein lysine acetylation has been classified into histone acetylation and non-histone protein acetylation. Histone acetylation is a kind of epigenetic modification, and it can modulate the transcription of important biological molecules in Wnt/β-catenin signaling. Additionally, as a type of post-translational modification, non-histone acetylation directly alters the function of the core molecules in Wnt/β-catenin signaling. Conversely, this signaling can regulate the expression and function of target molecules based on histone or non-histone protein acetylation. To date, various inhibitors targeting KATs and KDACs have been discovered, and some of these inhibitors exert their anti-tumor activity via blocking Wnt/β-catenin signaling. Here, we discuss the available evidence in understanding the complicated interaction of protein lysine acetylation with Wnt/β-catenin signaling, and lysine acetylation as a new target for cancer therapy via controlling this signaling.

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Section: Discussionmentioning

confidence: 99%

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

You

Kong

et al. 2022

Cell Mol Biol Lett

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“…The classical pathway is involved in cell survival, proliferation, differentiation and migration, while the non-classical pathway regulates cell polarity and migration. In addition to its biological role in development and homeostasis, the Wnt pathway is also involved in a variety of pathological diseases, including cancer [ 5 ]. The Wnt signaling cascade develops with multicellularity to coordinate the development and homeostasis of complex structures.…”

Section: Introductionmentioning

confidence: 99%

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

et al. 2022

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Background The Wnt signaling pathway is a complex network of protein interactions that functions most commonly in embryonic development and cancer, but is also involved in normal physiological processes in adults. The canonical Wnt signaling pathway regulates cell pluripotency and determines the differentiation fate of cells during development. The canonical Wnt signaling pathway (also known as the Wnt/β-catenin signaling pathway) is a recognized driver of colon cancer and one of the most representative signaling pathways. As a functional effector molecule of Wnt signaling, the modification and degradation of β-catenin are key events in the Wnt signaling pathway and the development and progression of colon cancer. Therefore, the Wnt signaling pathway plays an important role in the pathogenesis of diseases, especially the pathogenesis of colorectal cancer (CRC). Objective Inhibit the Wnt signaling pathway to explore the therapeutic targets of colorectal cancer. Methods Based on studying the Wnt pathway, master the biochemical processes related to the Wnt pathway, and analyze the relevant targets when drugs or inhibitors act on the Wnt pathway, to clarify the medication ideas of drugs or inhibitors for the treatment of diseases, especially colorectal cancer. Results Wnt signaling pathways include: Wnt/β-catenin or canonical Wnt signaling pathway, planar cell polarity (Wnt-PCP) pathway and Wnt-Ca2+ signaling pathway. The Wnt signaling pathway is closely related to cancer cell proliferation, stemness, apoptosis, autophagy, metabolism, inflammation and immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis. Drugs/phytochemicals and molecular preparations for the Wnt pathway of CRC treatment have now been developed. Wnt inhibitors are also commonly used clinically for the treatment of CRC. Conclusion The development of drugs/phytochemicals and molecular inhibitors targeting the Wnt pathway can effectively treat colorectal cancer clinically.

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“…The most common Wnt pathway mediated by LGR5 has been reported in many literatures, and it has been applied in breast cancer (Park et al, 2021;Neiheisel et al, 2022). In contrast, the literature shows that LGR5 reduces phosphorylation levels at Ser-1441/1443 of IQGAP1, resulting in increased binding of Rac1 to IQGAP1, thereby increasing cortical actin levels and enhancing normal cell-cancer cell adhesion.…”

Section: O N L I N E F I R S T a R T I C L Ementioning

confidence: 99%

Effect of Recombinant Glutathione-S-Transferase A3 Protein on the Expression of Host Defense Resistance and Pattern Recognition Receptor in the Thiram Induced Tibial Dyschondroplasia Chicken Erythrocytes

Mangi¹

2024

PJZ

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Wnt pathway modulators in cancer therapeutics: An update on completed and ongoing clinical trials

Cited by 62 publications

References 103 publications

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

Effect of Recombinant Glutathione-S-Transferase A3 Protein on the Expression of Host Defense Resistance and Pattern Recognition Receptor in the Thiram Induced Tibial Dyschondroplasia Chicken Erythrocytes

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