ArticleJournal of translational medicine2024
Effect of the mRNA decapping enzyme scavenger (DCPS) inhibitor RG3039 on glioblastoma.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Organoids as next-generation models for investigating intracranial tumours.Molecular brain · 2026Review
- Plasma extracellular vesicle proteomics nominates candidate biomarkers ofCell reports. Medicine · 2026Article
- N7-methylguanosine-related gene decapping scavenger enzymes as a novel biomarker regulating epithelial cell function in diabetic foot ulcers.World journal of diabetes · 2025Article
- Prognostic risk model of six m7 g-related lncRNAs in lung adenocarcinoma.European journal of medical research · 2025Article
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Authors and funding
18 authors.
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Abstract
backgroundPatients with glioblastoma (GBM) have a poor prognosis and limited treatment options. The mRNA decapping enzyme scavenger (DCPS) is a cap-hydrolyzing enzyme. The DCPS inhibitor RG3039 exhibited excellent central nervous system bioavailability in vivo and was safe and well tolerated in healthy volunteers in a phase 1 clinical trial. In this study, we investigated the expression of DCPS in GBM and the anti-tumor activity of RG3039 in various preclinical models of GBM.
methodsDCPS expression was examined in human GBM and paired peritumoral tissues. Its prognostic role was evaluated together with clinicopathological characteristics of patients. The anti-GBM effect of RG3039 was determined using GBM cell lines, patient-derived organoids, and orthotopic mouse models. The therapeutic mechanisms of DCPS inhibition were explored.
resultsDCPS is overexpressed in GBM and is associated with poor survival of patients with GBM. The DCPS inhibitor RG3039 exhibited robust anti-GBM activities in GBM cell lines, patient-derived organoids and orthotopic mouse models, with drug exposure achievable in humans. Mechanistically, RG3039 downregulated STAT5B expression, thereby suppressing proliferation, survival and colony formation of GBM cells.
conclusionsDCPS is a promising target for GBM. Inhibition of DCPS with RG3039 at doses achievable in humans downregulates STAT5B expression and reduces proliferation, survival and colony formation of GBM cells. Given the excellent anti-cancer activity and central nervous system bioavailability in vivo and good tolerance in humans, RG3039 warrants further study as a potential GBM therapy.
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