sr-3029 has been researched along with Breast-Neoplasms* in 1 studies
1 other study(ies) available for sr-3029 and Breast-Neoplasms
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Therapeutic targeting of casein kinase 1δ in breast cancer.
Identification of specific drivers of human cancer is required to instruct the development of targeted therapeutics. We demonstrate that CSNK1D is amplified and/or overexpressed in human breast tumors and that casein kinase 1δ (CK1δ) is a vulnerability of human breast cancer subtypes overexpressing this kinase. Specifically, selective knockdown of CK1δ, or treatment with a highly selective and potent CK1δ inhibitor, triggers apoptosis of CK1δ-expressing breast tumor cells ex vivo, tumor regression in orthotopic models of triple-negative breast cancer, including patient-derived xenografts, and tumor growth inhibition in human epidermal growth factor receptor 2-positive (HER2(+)) breast cancer models. We also show that Wnt/β-catenin signaling is a hallmark of human tumors overexpressing CK1δ, that disabling CK1δ blocks nuclear accumulation of β-catenin and T cell factor transcriptional activity, and that constitutively active β-catenin overrides the effects of inhibition or silencing of CK1δ. Thus, CK1δ inhibition represents a promising strategy for targeted treatment in human breast cancer with Wnt/β-catenin involvement. Topics: Animals; Antineoplastic Agents; Apoptosis; beta Catenin; Breast Neoplasms; Casein Kinase Idelta; Cell Proliferation; Computational Biology; Databases, Genetic; Dose-Response Relationship, Drug; Drug Design; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Mice, Nude; Mice, SCID; Molecular Targeted Therapy; Protein Kinase Inhibitors; Purines; RNA Interference; TCF Transcription Factors; Time Factors; Transfection; Triple Negative Breast Neoplasms; Tumor Burden; Wnt Signaling Pathway; Xenograft Model Antitumor Assays | 2015 |