Can we safely target the WNT pathway?
By M. Kahn. Nature reviews. Drug discovery, 2014
991 citations recorded by the source corpus.
WNT–β-catenin signalling is involved in a multitude of developmental processes and the maintenance of adult tissue homeostasis by regulating cell proliferation, differentiation, migration, genetic stability and apoptosis, as well as by maintaining adult stem cells in a pluripotent state. Not surprisingly, aberrant regulation of this pathway is therefore associated with a variety of diseases, including cancer, fibrosis and neurodegeneration. Despite this knowledge, therapeutic agents specifically targeting the WNT pathway have only recently entered clinical trials and none has yet been approved. This Review examines the problems and potential solutions to this vexing situation and attempts to bring them into perspective.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/d694275566e3e588a334719880c65712b57439ee
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Citations in the corpus
- Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities (2022, background): “In addition, the appropriate timing of drug administration is critical, particularly in patient stratification and drug delivery.(305,319,320) A more integrated experimental evaluation of mutations from different patient-derived tumours can be used to identify driver mutations from passenger mutatio”
- Wnt addiction of genetically defined cancers reversed by PORCN inhibition (2015, positive): “16,17 One approach is to target the secretion of all Wnts by inhibiting the enzymatic activity of Porcupine (PORCN), an ER resident enzyme that post-translationally palmitoleates Wnts at a highly conserved serine residue.”
- Targeting cancer stem cell pathways for cancer therapy (2020, background): “122 The Wnt signaling pathway can be divided into canonical Wnt signaling (through the FZD-LRP5/6 receptor complex, leading to derepression of β-catenin) and noncanonical Wnt signaling (through FZD receptors and/or ROR1/ROR2/RYK coreceptors, activating PCP, RTK, or Ca 2+ signaling cascades).”
- Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer (2021, methodology): “Wnt signaling pathway includes 19 Wnt ligands and more than 15 receptors, which can be classified into canonical and noncanonical signaling pathways.(116,180) In the canonical cascade, in the absence of Wnt ligands, cytoplasmic β-catenin combines with Axin complex and phosphorylates by glycogen synt”
- Wnt/ b -Catenin Signaling, Disease, and Emerging Therapeutic Modalities (2017, background): “In considering a widely used pathway such asWnt as a target for intervention, a concern arises from the predicted side effects of drugs (Kahn, 2014).”