ArticleFrontiers in oncology2015
Hedgehog Inhibitors in Rhabdomyosarcoma: A Comparison of Four Compounds and Responsiveness of Four Cell Lines.
Article in Frontiers in oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Towards directed therapy for fusion-positive rhabdomyosarcoma.Pharmacology & therapeutics · 2025Review
- Targeting developmental vulnerabilities in childhood sarcomas.Cancer metastasis reviews · 2025Review
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Targeting the Hedgehog Pathway in Rhabdomyosarcoma.Cancers · 2023Review
- Excellent Early Outcomes of Combined Chemotherapy With Arsenic Trioxide for Stage 4/M Neuroblastoma in Children: A Multicenter Nonrandomized Controlled Trial.Oncology research · 2021Article
- Context-dependent modulation of aggressiveness of pediatric tumors by individual oncogenic RAS isoforms.Oncogene · 2021Article
- Repurposing of posaconazole as a hedgehog/SMO signaling inhibitor for embryonal rhabdomyosarcoma therapy.American journal of cancer research · 2021Article
- Encouraging Early Outcomes of Treatment With Arsenic Trioxide Combined With Chemotherapy for Alveolar Rhabdomyosarcoma in Children: 4 Case Reports.Frontiers in oncology · 2021Article
- Loss of the PTCH1 tumor suppressor defines a new subset of plexiform fibromyxoma.Journal of translational medicine · 2019Article
- Genetics, epigenetics and redox homeostasis in rhabdomyosarcoma: Emerging targets and therapeutics.Redox biology · 2019Review
- Misactivation of Hedgehog signaling causes inherited and sporadic cancers.The Journal of clinical investigation · 2019Review
- Current and Future Treatment Strategies for Rhabdomyosarcoma.Frontiers in oncology · 2019Review
- Regulation and Role of GLI1 in Cutaneous Squamous Cell Carcinoma Pathogenesis.Frontiers in genetics · 2019Article
- Chemical, computational and functional insights into the chemical stability of the Hedgehog pathway inhibitor GANT61.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Hedgehog Signaling Pathway and Autophagy in Cancer.International journal of molecular sciences · 2018Review
- Reproducibility of academic preclinical translational research: lessons from the development of Hedgehog pathway inhibitors to treat cancer.Open biology · 2018Review
- Different Response ofFrontiers in oncology · 2018Article
- Pharmacological targeting of GLI1 inhibits proliferation, tumor emboli formation and in vivo tumor growth of inflammatory breast cancer cells.Cancer letters · 2017Article
- Phase I, multicenter, open-label, dose-escalation study of sonidegib in Asian patients with advanced solid tumors.Cancer science · 2016Article
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and is divided into two major histological subgroups, i.e., embryonal (ERMS) and alveolar RMS (ARMS). RMS can show HEDGEHOG/SMOOTHENED (HH/SMO) signaling activity and several clinical trials using HH inhibitors for therapy of RMS have been launched. We here compared the antitumoral effects of the SMO inhibitors GDC-0449, LDE225, HhA, and cyclopamine in two ERMS (RD, RUCH-2) and two ARMS (RMS-13, Rh41) cell lines. Our data show that the antitumoral effects of these SMO inhibitors are highly divers and do not necessarily correlate with inhibition of HH signaling. In addition, the responsiveness of the RMS cell lines to the drugs is highly heterogeneous. Whereas some SMO inhibitors (i.e., LDE225 and HhA) induce strong proapoptotic and antiproliferative effects in some RMS cell lines, others paradoxically induce cellular proliferation at certain concentrations (e.g., 10 μM GDC-0449 or 5 μM cyclopamine in RUCH-2 and Rh41 cells) or can increase HH signaling activity as judged by GLI1 expression (i.e., LDE225, HhA, and cyclopamine). Similarly, some drugs (e.g., HhA) inhibit PI3K/AKT signaling or induce autophagy (e.g., LDE225) in some cell lines, whereas others cannot (e.g., GDC-0449). In addition, the effects of SMO inhibitors are concentration-dependent (e.g., 1 and 10 μM GDC-0449 decrease GLI1 expression in RD cells whereas 30 μM GDC-0449 does not). Together these data show that some SMO inhibitors can induce strong antitumoral effects in some, but not all, RMS cell lines. Due to the highly heterogeneous response, we propose to conduct thorough pretesting of SMO inhibitors in patient-derived short-term RMS cultures or patient-derived xenograft mouse models before applying these drugs to RMS patients.
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