ArticleCancers2022
An FDA-Approved Antifungal, Ketoconazole, and Its Novel Derivative Suppress tGLI1-Mediated Breast Cancer Brain Metastasis by Inhibiting the DNA-Binding Activity of Brain Metastasis-Promoting Transcription Factor tGLI1.
Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Cancer Therapy Using Antiparasitic Medications Guided by Acupuncture Meridian Assessment: A Case Series of Six Patients.Integrative medicine (Encinitas, Calif.) · 2026Article
- RET receptor tyrosine kinase promotes breast cancer metastasis to the brain and RET inhibitors pralsetinib and selpercatinib suppress breast cancer brain metastases.Cell death & disease · 2026Article
- Old Drugs, New Battles: Unleashing Repurposed Drug Classes in Triple-Negative Breast Cancer Treatment.International journal of molecular sciences · 2025Review
- Targeting tGLI1, a novel mediator of tumor therapeutic resistance, using Ketoconazole sensitizes glioblastoma to CDK4/6 therapy and chemoradiation.bioRxiv : the preprint server for biology · 2025Article
- Article
- Harnessing Drug Repurposing to Combat Breast Cancer by Targeting Altered Metabolism and Epithelial-to-Mesenchymal Transition Pathways.ACS pharmacology & translational science · 2024Review
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- Glucocorticoid receptor: a harmonizer of cellular plasticity in breast cancer-directs the road towards therapy resistance, metastatic progression and recurrence.Cancer metastasis reviews · 2024Review
- Navigating the Blood-Brain Barrier: Challenges and Therapeutic Strategies in Breast Cancer Brain Metastases.International journal of molecular sciences · 2023Review
- Molecular signaling network and therapeutic developments in breast cancer brain metastasis.Advances in cancer biology - metastasis · 2023Article
- Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
The goal of this study is to identify pharmacological inhibitors that target a recently identified novel mediator of breast cancer brain metastasis (BCBM), truncated glioma-associated oncogene homolog 1 (tGLI1). Inhibitors of tGLI1 are not yet available. To identify compounds that selectively kill tGLI1-expressing breast cancer, we screened 1527 compounds using two sets of isogenic breast cancer and brain-tropic breast cancer cell lines engineered to stably express the control, GLI1, or tGLI1 vector, and identified the FDA-approved antifungal ketoconazole (KCZ) to selectively target tGLI1-positive breast cancer cells and breast cancer stem cells, but not tGLI1-negative breast cancer and normal cells. KCZ's effects are dependent on tGLI1. Two experimental mouse metastasis studies have demonstrated that systemic KCZ administration prevented the preferential brain metastasis of tGLI1-positive breast cancer and suppressed the progression of established tGLI1-positive BCBM without liver toxicities. We further developed six KCZ derivatives, two of which (KCZ-5 and KCZ-7) retained tGLI1-selectivity in vitro. KCZ-7 exhibited higher blood-brain barrier penetration than KCZ/KCZ-5 and more effectively reduced the BCBM frequency. In contrast, itraconazole, another FDA-approved antifungal, failed to suppress BCBM. The mechanistic studies suggest that KCZ and KCZ-7 inhibit tGLI1's ability to bind to DNA, activate its target stemness genes
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.