ArticleMolecular cancer therapeutics2010
Molecular therapy targeting Sonic hedgehog and hepatocyte growth factor signaling in a mouse model of medulloblastoma.
Article in Molecular cancer therapeutics, 2010. 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, 40 citations in OpenAlex.
- Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications.Molecular brain · 2024Review
- Unravelling the Mysteries of the Sonic Hedgehog Pathway in Cancer Stem Cells: Activity, Crosstalk and Regulation.Current issues in molecular biology · 2024Review
- Therapeutic implication of Sonic Hedgehog as a potential modulator in ischemic injury.Pharmacological reports : PR · 2023Review
- Review
- Profiling and targeting cancer stem cell signaling pathways for cancer therapeutics.Frontiers in cell and developmental biology · 2023Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Cancer Metastasis and Treatment Resistance: Mechanistic Insights and Therapeutic Targeting of Cancer Stem Cells and the Tumor Microenvironment.Biomedicines · 2022Review
- Hedgehog signaling underlying tendon and enthesis development and pathology.Matrix biology : journal of the International Society for Matrix Biology · 2022Review
- The hepatocyte growth factor/mesenchymal epithelial transition factor axis in high-risk pediatric solid tumors and the anti-tumor activity of targeted therapeutic agents.Frontiers in pediatrics · 2022Review
- Blocking SHH/Patched Interaction Triggers Tumor Growth Inhibition through Patched-Induced Apoptosis.Cancer research · 2020Article
- Safety and Tolerability of Sonic Hedgehog Pathway Inhibitors in Cancer.Drug safety · 2019Review
- Development of anticancer agents targeting the Hedgehog signaling.Cellular and molecular life sciences : CMLS · 2017Review
- Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment.Cancers · 2017Review
- Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors.Cancers · 2016Review
- Somatic cell transfer of c-Myc and Bcl-2 induces large-cell anaplastic medulloblastomas in mice.Journal of neuro-oncology · 2016Article
- MiR-338* targeting smoothened to inhibit pulmonary fibrosis by epithelial-mesenchymal transition.American journal of translational research · 2016Article
- Medulloblastoma development: tumor biology informs treatment decisions.CNS oncology · 2015Review
- miRNA-338-3p suppresses cell growth of human colorectal carcinoma by targeting smoothened.World journal of gastroenterology · 2013Article
- Off-target function of the Sonic hedgehog inhibitor cyclopamine in mediating apoptosis via nitric oxide-dependent neutral sphingomyelinase 2/ceramide induction.Molecular cancer therapeutics · 2012Article
- Matching mice to malignancy: molecular subgroups and models of medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2012Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The use of genetically engineered mice has provided insights into the molecular pathogenesis of the pediatric brain tumor medulloblastoma and revealed promising therapeutic targets. Ectopic expression of Sonic hedgehog (Shh) in cerebellar neural progenitor cells induces medulloblastomas in mice, and coexpression of hepatocyte growth factor (HGF) enhances Shh-induced tumor formation. To determine whether Shh + HGF-driven medulloblastomas were responsive to Shh signaling blockade and whether treatment response could be enhanced by combination therapy targeting both HGF and Shh signaling pathways, we carried out a survival study in mice. We induced medulloblastomas by retrovirus-mediated expression of Shh and HGF, after which we treated the mice systemically with (a) HGF-neutralizing monoclonal antibody L2G7, (b) Shh signaling inhibitor cyclopamine, (c) Shh-neutralizing monoclonal antibody 5E1, (d) L2G7 + cyclopamine, or (e) L2G7 + 5E1. We report that monotherapy targeting either HGF signaling or Shh signaling prolonged survival and that anti-HGF therapy had a more durable response than Shh-targeted therapy. The effect of L2G7 + 5E1 combination therapy on cumulative survival was equivalent to that of L2G7 monotherapy and that of L2G7 + cyclopamine therapy was worse. The principal mechanism by which Shh- and HGF-targeted therapies inhibited tumor growth was a potent apoptotic death response in tumor cells, supplemented by a weaker suppressive effect on proliferation. Our observation that combination therapy either failed to improve or even reduced survival in mice bearing Shh + HGF-induced medulloblastomas compared with monotherapy underscores the importance of preclinical testing of molecular-targeted therapies in animal models of tumors in which the targeted pathways are known to be active.
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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.