ArticleMolecular cancer therapeutics2016
Posaconazole, a Second-Generation Triazole Antifungal Drug, Inhibits the Hedgehog Signaling Pathway and Progression of Basal Cell Carcinoma.
Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 60 citations in OpenAlex.
- MEVITEM-a phase I/II trial of vismodegib + temozolomide vs temozolomide in patients with recurrent/refractory medulloblastoma with Sonic Hedgehog pathway activation.Neuro-oncology · 2021Trial
- From fungus fighter to cancer slayer: itraconazole as a multifaceted candidate for drug-resistant prostate cancer.Prostate cancer and prostatic diseases · 2026Review
- Understanding the impact of triazoles on female fertility and embryo development: Mechanisms and implications.Toxicology reports · 2025Review
- Perturbing local steroidogenesis to improve breast cancer immunity.Nature communications · 2025Article
- Identification of Potent Zika Virus NS5 RNA-Dependent RNA Polymerase Inhibitors Combining Virtual Screening and Biological Assays.International journal of molecular sciences · 2023Article
- Glioblastoma: Current Status, Emerging Targets, and Recent Advances.Journal of medicinal chemistry · 2022Review
- Tumor microenvironment pathways: Cross regulation in breast cancer metastasis.Genes & diseases · 2022Review
- Sterol regulation of developmental and oncogenic Hedgehog signaling.Biochemical pharmacology · 2022Review
- The Role of the Hedgehog Pathway in Cholangiocarcinoma.Cancers · 2021Review
- The antifungal drug isavuconazole inhibits the replication of human cytomegalovirus (HCMV) and acts synergistically with anti-HCMV drugs.Antiviral research · 2021Article
- Distinct transcriptomic landscapes of cutaneous basal cell carcinomas and squamous cell carcinomas.Genes & diseases · 2021Article
- Repurposing of posaconazole as a hedgehog/SMO signaling inhibitor for embryonal rhabdomyosarcoma therapy.American journal of cancer research · 2021Article
- Sterols in an intramolecular channel of Smoothened mediate Hedgehog signaling.Nature chemical biology · 2020Article
- The Clinically Approved Antifungal Drug Posaconazole Inhibits Human Cytomegalovirus Replication.Antimicrobial agents and chemotherapy · 2020Article
- Mechanistic Insights into the Generation and Transduction of Hedgehog Signaling.Trends in biochemical sciences · 2020Review
- Biallelic PTCH1 Inactivation Is a Dominant Genomic Change in Sporadic Keratocystic Odontogenic Tumors.The American journal of surgical pathology · 2020Article
- Article
- Sonic Hedgehog Pathway Inhibition in the Treatment of Advanced Basal Cell Carcinoma.Current treatment options in oncology · 2019Review
- Review
- Role of Protein Kinases in Hedgehog Pathway Control and Implications for Cancer Therapy.Cancers · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Deregulation of Hedgehog (Hh) pathway signaling has been associated with the pathogenesis of various malignancies, including basal cell carcinomas (BCC). Inhibitors of the Hh pathway currently available or under clinical investigation all bind and antagonize Smoothened (SMO), inducing a marked but transient clinical response. Tumor regrowth and therapy failure were attributed to mutations in the binding site of these small-molecule SMO antagonists. The antifungal itraconazole was demonstrated to be a potent SMO antagonist with a distinct mechanism of action from that of current SMO inhibitors. However, itraconazole represents a suboptimal therapeutic option due to its numerous drug-drug interactions. Here, we show that posaconazole, a second-generation triazole antifungal with minimal drug-drug interactions and a favorable side-effect profile, is also a potent inhibitor of the Hh pathway that functions at the level of SMO. We demonstrate that posaconazole inhibits the Hh pathway by a mechanism distinct from that of cyclopamine and other cyclopamine-competitive SMO antagonists but, similar to itraconazole, has robust activity against drug-resistant SMO mutants and inhibits the growth of Hh-dependent BCC in vivo Our results suggest that posaconazole, alone or in combination with other Hh pathway antagonists, may be readily tested in clinical studies for the treatment of Hh-dependent cancers. Mol Cancer Ther; 15(5); 866-76. ©2016 AACR.
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