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Ref Type Journal Article
PMID (25660951)
Authors Jang GB, Hong IS, Kim RJ, Lee SY, Park SJ, Lee ES, Park JH, Yun CH, Chung JU, Lee KJ, Lee HY, Nam JS
Title Wnt/β-Catenin Small-Molecule Inhibitor CWP232228 Preferentially Inhibits the Growth of Breast Cancer Stem-like Cells.
Journal Vol Issue Date Pages Journal Short Title
Cancer research 75 8 2015 Apr 15 1691-702 Cancer Res
URL
Abstract Text Breast cancer stem cells (BCSC) are resistant to conventional chemotherapy and radiotherapy, which may destroy tumor masses but not all BCSC that can mediate relapses. In the present study, we showed that the level of Wnt/β-catenin signaling in BCSC is relatively higher than in bulk tumor cells, contributing to a relatively higher level of therapeutic resistance. We designed a highly potent small-molecule inhibitor, CWP232228, which antagonizes binding of β-catenin to T-cell factor (TCF) in the nucleus. Notably, although CWP232228 inhibited the growth of both BCSC and bulk tumor cells by inhibiting β-catenin-mediated transcription, BCSC exhibited greater growth inhibition than bulk tumor cells. We also documented evidence of greater insulin-like growth factor-I (IGF-I) expression by BCSC than by bulk tumor cells and that CWP232228 attenuated IGF-I-mediated BCSC functions. These results suggested that the inhibitory effect of CWP232228 on BCSC growth might be achieved through the disruption of IGF-I activity. Taken together, our findings indicate that CWP232228 offers a candidate therapeutic agent for breast cancer that preferentially targets BCSC as well as bulk tumor cells.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
CWP232228 CWP232228 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
CWP232228 HY-18959|CS-0014678 CTNNB1 Inhibitor 27 CWP232228 is a small molecule that inhibits binding of CTNNB1 to TCF, resulting in decreased Wnt signaling and inhibition of tumor growth (PMID: 25660951, PMID: 31262892).
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