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Ref Type Journal Article
PMID (28951456)
Authors Yang A, Qin S, Schulte BA, Ethier SP, Tew KD, Wang GY
Title MYC Inhibition Depletes Cancer Stem-like Cells in Triple-Negative Breast Cancer.
Journal Vol Issue Date Pages Journal Short Title
Cancer research 77 23 2017 12 01 6641-6650 Cancer Res
URL
Abstract Text There is mounting evidence that cancer stem-like cells (CSC) are selectively enriched in residual tumors after anticancer therapies, which may account for tumor recurrence and metastasis by regenerating new tumors. Thus, there is a critical need to develop new therapeutic agents that can effectively eliminate drug-resistant CSCs and improve the efficacy of cancer therapy. Here, we report that Triptolide (C1572), a small-molecule natural product, selectively depletes CSCs in a dose-dependent fashion in human triple-negative breast cancer (TNBC) cell lines. Nanomolar concentrations of C1572 markedly reduced c-MYC (MYC) protein levels via a proteasome-dependent mechanism. Silencing MYC expression phenocopied the CSC depletion effects of C1572 and induced senescence in TNBC cells. Limited dilution assays revealed that ex vivo treatment of TNBC cells with C1572 reduced CSC levels by 28-fold. In mouse xenograft models of human TNBC, administration of C1572 suppressed tumor growth and depleted CSCs in a manner correlated with diminished MYC expression in residual tumor tissues. Together, these new findings provide a preclinical proof of concept defining C1572 as a promising therapeutic agent to eradicate CSCs for drug-resistant TNBC treatment. Cancer Res; 77(23); 6641-50. ©2017 AACR.

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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
Triptolide Triptolide 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Triptolide C1572 Triptolide (C1572) is a plant-derived small molecule that reduces MYC protein expression, and may decrease cancer stem cell number and tumor growth (PMID: 28951456, PMID: 32775615).
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