ArticleOncogene2005
Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi's sarcoma tumor cells.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01236586 (A Phase 1/2 Study of RO4929097, An Oral Small Molecule Inhibitor of Gamma-Secretase, in Children With Relapsed/Refractory Solid or CNS Tumors, Lymphoma, or T-Cell Leukemia), which is not on this map. Cited by 96 papers.
What it found
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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.
A Phase 1/2 Study of RO4929097, An Oral Small Molecule Inhibitor of Gamma-Secretase, in Children With Relapsed/Refractory Solid or CNS Tumors, Lymphoma, or T-Cell Leukemia
Who cites it
96 citing papers in PubMed, 211 citations in OpenAlex.
- Towards Cost-Effective and Sustainable Media Formulations for Terrestrial and Aquatic Cellular Agriculture.Foods (Basel, Switzerland) · 2026Review
- Review
- Repurposing nirogacestat, a gamma secretase enzyme inhibitor in desmoid tumors.Future oncology (London, England) · 2025Review
- The role of YTHDF1 in the diagnosis and prognosis of lung adenocarcinoma and its inhibitor LY-411575 in the targeted intervention of lung adenocarcinoma growth.Translational cancer research · 2025Article
- The cellular Notch1 protein promotes KSHV reactivation in an Rta-dependent manner.Journal of virology · 2024Article
- Normalization of Snai1-mediated vessel dysfunction increases drug response in cancer.Oncogene · 2024Article
- A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy.Nature communications · 2024Article
- Onco-Pathogen Mediated Cancer Progression and Associated Signaling Pathways in Cancer Development.Pathogens (Basel, Switzerland) · 2023Review
- The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics.International journal of biological sciences · 2023Review
- Recent Advances and Current Management for Desmoid Tumor Associated with Familial Adenomatous Polyposis.Journal of the anus, rectum and colon · 2023Review
- Notch regulates Histoplasma capsulatum clearance in mouse lungs during innate and adaptive immune response phases in primary infection.Journal of leukocyte biology · 2022Article
- Signaling pathways and their potential therapeutic utility in esophageal squamous cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Kaposi's sarcoma-associated herpesvirus infection promotes proliferation of SH-SY5Y cells by the Notch signaling pathway.Cancer cell international · 2021Article
- Gamma Secretase Inhibitors in Cancer: A Current Perspective on Clinical Performance.The oncologist · 2021Review
- Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy.Molecules (Basel, Switzerland) · 2021Review
- When Viruses Cross Developmental Pathways.Frontiers in cell and developmental biology · 2021Review
- Cancer Stem Cells,Cells · 2020Review
- Dibenzazepine Attenuates Against Cisplatin-Induced Nephrotoxicity in Rats: Involvement of NOTCH Pathway.Frontiers in pharmacology · 2020Article
- A herpesvirus transactivator and cellular POU proteins extensively regulate DNA binding of the host Notch signaling protein RBP-Jκ to the virus genome.The Journal of biological chemistry · 2019Article
- Notch Signaling Inhibition by LY411575 Attenuates Osteoblast Differentiation and Decreased Ectopic Bone Formation Capacity of Human Skeletal (Mesenchymal) Stem Cells.Stem cells international · 2019Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Kaposi's sarcoma (KS) is a common neoplasm in HIV-1-infected individuals causing significant morbidity and mortality. Despite recent advances, the pathogenesis of this potentially life-threatening neoplasm remains unclear, and there is currently no cure for KS. Notch proteins are known to play a fundamental role in cell fate decisions including proliferation, differentiation, and apoptosis. It is, therefore, not surprising that Notch proteins have been implicated in tumorigenesis and appear to function as either oncogenes or tumor suppressor proteins depending on cellular context. In this report, we demonstrate elevated levels of activated Notch-1, -2, and -4 in KS tumor cells in vivo and in vitro compared to endothelial cells, the precursor of the KS cell. Notch activation was confirmed through luciferase reporter assays and localization of Hes (Hairy/Enhancer of Split)-1 and Hey (Hairy/Enhancer of Split related with YRPW)1 (primary targets of the Notch pathway) in KS cell nuclei. Studies using gamma-secretase inhibitors (GSI and LY-411,575), which block Notch activation, resulted in apoptosis in primary and immortalized KS cells. Similar studies injecting GSI into established KS cell tumors on mice demonstrated growth inhibition or tumor regression that was characterized by apoptosis in treated, but not control tumors. The results indicate that KS cells overexpress activated Notch and interruption of Notch signaling inhibits KS cell growth. Thus, targeting Notch signaling may be of therapeutic value in KS patients.
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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.