ArticleOncotarget2014
GLI inhibitor GANT-61 diminishes embryonal and alveolar rhabdomyosarcoma growth by inhibiting Shh/AKT-mTOR axis.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 89 citations in OpenAlex.
- Circulating Tumor Cells in Soft Tissue Sarcoma: Current Evidence and Clinical Implications.Cancers · 2026Review
- Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy.Cells · 2024Review
- Unravelling the Mysteries of the Sonic Hedgehog Pathway in Cancer Stem Cells: Activity, Crosstalk and Regulation.Current issues in molecular biology · 2024Review
- Soft Tissue Sarcomas with Chromosomal Alterations in the 12q13-15 Region: Differential Diagnosis and Therapeutic Implications.Cancers · 2024Review
- Article
- The Hedgehog Pathway as a Therapeutic Target in Chronic Myeloid Leukemia.Pharmaceutics · 2023Review
- Combined inhibition of BET bromodomain and mTORC1/2 provides therapeutic advantage for rhabdomyosarcoma by switching cell death mechanism.Molecular carcinogenesis · 2022Article
- Advances in glioma-associated oncogene (GLI) inhibitors for cancer therapy.Investigational new drugs · 2022Review
- Review
- Reversion of methionine addiction of osteosarcoma cells to methionine independence results in loss of malignancy, modulation of the epithelial-mesenchymal phenotype and alteration of histone-H3 lysine-methylation.Frontiers in oncology · 2022Article
- Molecular mechanisms underpinning sarcomas and implications for current and future therapy.Signal transduction and targeted therapy · 2021Review
- The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair.eLife · 2021Article
- 5'-Cap‒Dependent Translation as a Potent Therapeutic Target for Lethal Human Squamous Cell Carcinoma.The Journal of investigative dermatology · 2021Article
- Targeting Hedgehog signalling in CD133-positive hepatocellular carcinoma: improving Lenvatinib therapeutic efficiency.Medical oncology (Northwood, London, England) · 2021Article
- Molecular Targets for Novel Therapeutics in Pediatric Fusion-Positive Non-CNS Solid Tumors.Frontiers in pharmacology · 2021Review
- GEFT Inhibits Autophagy and Apoptosis in RhabdomyosarcomaFrontiers in oncology · 2021Article
- Article
- GLI1 activation is a key mechanism of erlotinib resistance in human non-small cell lung cancer.Oncology letters · 2020Article
- GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells.International journal of molecular sciences · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Rhabdomyosarcoma (RMS) typically arises from skeletal muscle. Currently, RMS in patients with recurrent and metastatic disease have no successful treatment. The molecular pathogenesis of RMS varies based on cancer sub-types. Some embryonal RMS but not other sub-types are driven by sonic hedgehog (Shh) signaling pathway. However, Shh pathway inhibitors particularly smoothened inhibitors are not highly effective in animals. Here, we show that Shh pathway effectors GLI1 and/or GLI2 are over-expressed in the majority of RMS cells and that GANT-61, a specific GLI1/2 inhibitor dampens the proliferation of both embryonal and alveolar RMS cells-derived xenograft tumors thereby blocking their growth. As compared to vehicle-treated control, about 50% tumor growth inhibition occurs in mice receiving GANT-61 treatment. The proliferation inhibition was associated with slowing of cell cycle progression which was mediated by the reduced expression of cyclins D1/2/3 & E and the concomitant induction of p21. GANT-61 not only reduced expression of GLI1/2 in these RMS but also significantly diminished AKT/mTOR signaling. The therapeutic action of GANT-61 was significantly augmented when combined with chemotherapeutic agents employed for RMS therapy such as temsirolimus or vincristine. Finally, reduced expression of proteins driving epithelial mesenchymal transition (EMT) characterized the residual tumors.
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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.