New avenues to target Wnt/β-catenin signaling.
Wnt/β-catenin signaling is an evolutionarily conserved signaling cascade with imperative roles during development and in adult stem cell maintenance. Hyperactivation of Wnt/β-catenin drives various cancers, whereas hypoactivation underlies bone malformations and neurodegenerative disorders. Although several small molecule modulators of Wnt/β-catenin signaling have been identified, none have progressed into clinical trials yet. Recent studies employing genomics and proteomics approaches have yielded more druggable targets, such as kinases and seven-transmembrane receptors. In addition, new assay methods enable a more targeted approach for high-throughput screening of this pathway and are expected to deliver clinical candidates in the coming decade.
Merck Research Laboratories, MSD, Molecular Pharmacology & DMPK, PO Box 20, 5340 BH Oss, The Netherlands.
Folkert
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Verkaar
Guido J R
GJ
Zaman
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D051153:Wnt Proteins; D051176:beta Catenin