ArticleCell death & disease2021
BKM120 sensitizes glioblastoma to the PARP inhibitor rucaparib by suppressing homologous recombination repair.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 77 citations in OpenAlex.
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- In Vitro Evaluation of PARP1 Inhibitor Olaparib-Cyanine Dye Conjugate for the Treatment of Glioblastoma.ChemMedChem · 2026Article
- The Antihistamine Astemizole Potentiates the Antitumor Efficacy of Sorafenib in Hepatocellular Carcinoma by Suppressing Proliferation, Metastasis, and Angiogenesis.Current issues in molecular biology · 2026Article
- Enhancing Chemotherapeutic Efficacy in Lung Cancer Cells Through Synergistic Targeting of the PI3K/AKT Pathway with Small Molecule Inhibitors.International journal of molecular sciences · 2025Article
- Jab1 regulates HRR mRNA stability to modulate PARP inhibitor sensitivity in triple-negative breast cancer.Molecular cancer · 2025Article
- Antitumor effect of BC12-3 on multiple myeloma via proteasome inhibition.Medical oncology (Northwood, London, England) · 2025Article
- Synthesis and Characterization of Transferrin Receptor-Targeted Peptide Combination SN-38 and Rucaparib Conjugate for the Treatment of Glioblastoma.Pharmaceutics · 2025Article
- PARP inhibitor response is enhanced in prostate cancer when XRCC1 expression is reduced.NAR cancer · 2025Article
- Post-translational modifications in DNA damage repair: mechanisms underlying temozolomide resistance in glioblastoma.Oncogene · 2025Review
- Review
- SIK2 inhibitor SIC-19 enhances the sensitivity of PARP inhibitors in triple-negative breast cancers and pancreatic cancers.Oncology research · 2025Article
- Article
- Sequential Inhibition of PARP and BET as a Rational Therapeutic Strategy for Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The combination of temozolomide and perifosine synergistically inhibit glioblastoma by impeding DNA repair and inducing apoptosis.Cell death discovery · 2024Article
- A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation.Molecular cancer · 2024Article
- Flavopiridol Suppresses Cell Proliferation and Migration and Induces Apoptotic Cell Death by Inhibiting Oncogenic FOXM1 Signaling in IDH Wild-Type and IDH-Mutant GBM Cells.Molecular neurobiology · 2024Article
- KPT330 promotes the sensitivity of glioblastoma to olaparib by retaining SQSTM1 in the nucleus and disrupting lysosomal function.Autophagy · 2024Article
- HSPA5 and FGFR1 genes in the mesenchymal subtype of glioblastoma can improve a treatment efficacy.Animal cells and systems · 2024Article
- Unveiling Novel Avenues in mTOR-Targeted Therapeutics: Advancements in Glioblastoma Treatment.International journal of molecular sciences · 2023Review
- Targeting CK2-mediated phosphorylation of p53R2 sensitizes BRCA-proficient cancer cells to PARP inhibitors.Oncogene · 2023Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
PARP inhibitors have been approved for the therapy of cancers with homologous recombination (HR) deficiency based on the concept of "synthetic lethality". However, glioblastoma (GBM) patients have gained little benefit from PARP inhibitors due to a lack of BRCA mutations. Herein, we demonstrated that concurrent treatment with the PARP inhibitor rucaparib and the PI3K inhibitor BKM120 showed synergetic anticancer effects on GBM U251 and U87MG cells. Mechanistically, BKM120 decreased expression of HR molecules, including RAD51 and BRCA1/2, and reduced HR repair efficiency in GBM cells, therefore increasing levels of apoptosis induced by rucaparib. Furthermore, we discovered that the two compounds complemented each other in DNA damage response and drug accumulation. Notably, in the zebrafish U87MG-RFP orthotopic xenograft model, nude mouse U87MG subcutaneous xenograft model and U87MG-Luc orthotopic xenograft model, combination showed obviously increased antitumor efficacy compared to each monotherapy. Immunohistochemical analysis of tumor tissues indicated that the combination obviously reduced expression of HR repair molecules and increased the DNA damage biomarker γ-H2AX, consistent with the in vitro results. Collectively, our findings provide new insight into combined blockade of PI3K and PARP, which might represent a promising therapeutic approach for GBM.
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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.