ArticleInternational journal of cancer2018
Targeting class I histone deacetylases by the novel small molecule inhibitor 4SC-202 blocks oncogenic hedgehog-GLI signaling and overcomes smoothened inhibitor resistance.
Article in International journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Transforming Outcomes in Advanced Basal Cell Carcinoma: The Evolving Role of Systemic Therapy.American journal of clinical dermatology · 2026Review
- Epigenetic marvels: exploring the landscape of colorectal cancer treatment through cutting-edge epigenetic-based drug strategies.Clinical epigenetics · 2025Review
- SIN3B Loss Heats up Cold Tumor Microenvironment to Boost Immunotherapy in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Novel Histone Deacetylase (HDAC) Inhibitor Induces Apoptosis and Suppresses Invasion via E-Cadherin Upregulation in Pancreatic Ductal Adenocarcinoma (PDAC).Pharmaceuticals (Basel, Switzerland) · 2024Article
- Investigation of the effect of belinostat on MCF-7 breast cancer stem cells via the Wnt, Notch, and Hedgehog signaling pathway.Saudi medical journal · 2024Article
- Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer.Acta pharmaceutica Sinica. B · 2023Article
- 4SC-202 exerts an anti-tumor effect in cervical cancer by targeting PRLR signaling pathway.Journal of molecular histology · 2022Article
- Can We Efficiently Target HDAC in Cancer?Cancers · 2022Article
- HDAC Class I Inhibitor Domatinostat Preferentially Targets Glioma Stem Cells over Their Differentiated Progeny.International journal of molecular sciences · 2022Article
- HDAC class I inhibitor domatinostat sensitizes pancreatic cancer to chemotherapy by targeting cancer stem cell compartment via FOXM1 modulation.Journal of experimental & clinical cancer research : CR · 2022Article
- Hedgehog/GLI signaling in hematopoietic development and acute myeloid leukemia-From bench to bedside.Frontiers in cell and developmental biology · 2022Review
- Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma.Oncotarget · 2021Review
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- Inhibition of EZH2 by chidamide exerts antileukemia activity and increases chemosensitivity through Smo/Gli-1 pathway in acute myeloid leukemia.Journal of translational medicine · 2021Article
- MTOR promotes basal cell carcinoma growth through atypical PKC.Experimental dermatology · 2021Article
- PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation.Frontiers in oncology · 2021Article
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- Article
- 4SC-202 induces apoptosis in myelodysplastic syndromes and the underlying mechanism.American journal of translational research · 2020Article
- KCTD15 inhibits the Hedgehog pathway in Medulloblastoma cells by increasing protein levels of the oncosuppressor KCASH2.Oncogenesis · 2019Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activation of Hedgehog (HH)/GLI signaling is causally involved in numerous human malignancies, including basal cell carcinoma (BCC) and medulloblastoma. HH pathway antagonists targeting smoothened (SMO), an essential effector of canonical HH/GLI signaling, show significant clinical success in BCC patients and have recently been approved for the treatment of advanced and metastatic BCC. However, rapid and frequent development of drug resistance to SMO inhibitors (SMOi) together with severe side effects caused by prolonged SMOi treatment call for alternative treatment strategies targeting HH/GLI signaling downstream of SMO. In this study, we report that 4SC-202, a novel clinically validated inhibitor of class I histone deacetylases (HDACs), efficiently blocks HH/GLI signaling. Notably, 4SC-202 treatment abrogates GLI activation and HH target gene expression in both SMOi-sensitive and -resistant cells. Mechanistically, we propose that the inhibition of HDACs 1/2/3 is crucial for targeting oncogenic HH/GLI signaling, and that class I HDAC inhibitors either in combination with SMOi or as second-line therapy may improve the treatment options for HH-associated malignancies with SMOi resistance.
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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.