ArticleInternational journal of molecular sciences2021
Novel Dual PI3K/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- Thieno[3,2-International journal of molecular sciences · 2026Review
- Integrated Multi-Omics and Spatial Transcriptomics Reveal GUK1 as a Prognostic Biomarker Regulated by the TP53-HSF1 Axis in Breast Cancer.Oncology research · 2026Article
- Targeting EGFR and PI3K/mTOR pathways in glioblastoma: innovative therapeutic approaches.Medical oncology (Northwood, London, England) · 2025Review
- Phospholipase C Beta 2 as a Key Regulator of Tumor Progression and Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Renal Cell Carcinoma.Biomedicines · 2025Article
- The Impact of Metabolic Rewiring in Glioblastoma: The Immune Landscape and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Review
- Regulation of PI3K signaling in cancer metabolism and PI3K-targeting therapy.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2024Review
- Targeted Inhibition of the PI3K/Akt/mTOR Signaling Axis: Potential for Sarcoma Therapy.Mini reviews in medicinal chemistry · 2024Review
- Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK).Journal of enzyme inhibition and medicinal chemistry · 2023Review
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- Clinical and molecular analysis of cilia-associated gene signature for prognostic prediction in glioma.Journal of cancer research and clinical oncology · 2023Article
- Recent advances in targeted strategies for triple-negative breast cancer.Journal of hematology & oncology · 2023Review
- Review
- Recurrent Glioblastoma: Ongoing Clinical Challenges and Future Prospects.OncoTargets and therapy · 2023Review
- Integrative genomic analysis facilitates precision strategies for glioblastoma treatment.iScience · 2022Article
- mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer.International journal of molecular sciences · 2022Review
- Metabolomic and Lipidomic Profiling of Gliomas-A New Direction in Personalized Therapies.Cancers · 2022Review
- Mechanism of the Huangguoshu waterfall forest environment's promotive effect on human health in Guizhou, China.Annals of translational medicine · 2022Article
- Development of New Thiophene-Containing Triaryl Pyrazoline Derivatives as PI3Kγ Inhibitors.Molecules (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulated PI3K/AKT/mTOR signalling commonly exists in glioblastoma, making this axis an attractive target for therapeutic manipulation. Given that activation of PI3K/AKT/mTOR promotes tumour growth, metastasis, and resistance to anticancer therapies, mTOR inhibitors show promise in the treatment of cancer. The aim of this study was to investigate the underlying mechanism of novel dual PI3K/mTOR inhibitor, Apitolisib (GDC-0980), in A-172 and U-118-MG GBM tumour cell line suppression. It has been demonstrated that GDC-0980 induces time- and dose-dependent cytotoxicity and apoptosis in investigated glioma cell lines. In our study, the strongest induction of apoptosis was exhibited in the A-172 line after 48 h of incubation with 20 µM GDC-0980, where we observed 46.47% of apoptotic cells. In conclusion, we first discovered that dual PI3K/mTOR blockade by GDC-0980 markedly suppressed survival of human GBM cells and induced apoptosis, independent of the ER stress-mediated DR5 activation. We suggest that GDC-0980, by exerting an inhibitory effect on PERK expression, may thus block its inhibitory effect on protein synthesis, leading to intensification of translation, and this may result in an increase in apoptosis. On the other hand, CHOP stimulates protein synthesis and increases apoptosis. These findings suggest that GDC-0980 may be a candidate for further evaluation as a chemotherapeutic agent for anti-GBM therapy.
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