Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : firstname.lastname@example.org
|Ref Type||Journal Article|
|Authors||Gonsalves FC, Klein K, Carson BB, Katz S, Ekas LA, Evans S, Nagourney R, Cardozo T, Brown AM, DasGupta R|
|Title||An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of the Wnt/wingless signaling pathway.|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Date||2011 Apr 12|
|Abstract Text||Misregulated β-catenin responsive transcription (CRT) has been implicated in the genesis of various malignancies, including colorectal carcinomas, and it is a key therapeutic target in combating various cancers. Despite significant effort, successful clinical implementation of CRT inhibitory therapeutics remains a challenging goal. This is, in part, because of the challenge of identifying inhibitory compounds that specifically modulate the nuclear transcriptional activity of β-catenin while not affecting its cytoskeletal function in stabilizing adherens junctions at the cell membrane. Here, we report an RNAi-based modifier screening strategy for the identification of CRT inhibitors. Our data provide support for the specificity of these inhibitory compounds in antagonizing the transcriptional function of nuclear β-catenin. We show that these inhibitors efficiently block Wnt/β-catenin-induced target genes and phenotypes in various mammalian and cancer cell lines. Importantly, these Wnt inhibitors are specifically cytotoxic to human colon tumor biopsy cultures as well as colon cancer cell lines that exhibit deregulated Wnt signaling.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|APC inact mut||colon cancer||sensitive||iCRT-14||Preclinical - Cell line xenograft||Actionable||In a preclinical study, iCRT-14 induced cell-cycle arrest and inhibited proliferation of colon cancer cells harboring APC inactivating mutations in culture and decreased initial tumor growth in APC-mutant colon cancer cell line xenograft models (PMID: 21393571).||21393571|
|APC inact mut||colon cancer||sensitive||iCRT-3||Preclinical||Actionable||In a preclinical study, iCRT-3 induced cell-cycle arrest and inhibited proliferation of colon cancer cells harboring APC inactivating mutations in culture (PMID: 21393571).||21393571|
|APC inact mut||colon cancer||sensitive||iCRT-5||Preclinical||Actionable||In a preclinical study, iCRT-5 induced cell-cycle arrest and inhibited proliferation of colon cancer cells harboring APC inactivating mutations in culture (PMID: 21393571).||21393571|