ArticleCell death & disease2021
Glycogen synthase kinase 3β inhibition synergizes with PARP inhibitors through the induction of homologous recombination deficiency in colorectal cancer.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Expanding Synthetic Lethality in DNA Damage Response-Defective Cancers Through Stress Phenotype-Guided Kinase Targeting.International journal of molecular sciences · 2026Review
- Identification of RRM2 as a key regulator of malignant epithelial cells in gastric cancer through single‑cell transcriptomics.Oncology reports · 2026Article
- GSK3βGut · 2026Article
- Discovery of Supra-Bivalent GSK3β Inhibitory Peptides Containing an ATP-Mimetic Amino Acid.Journal of the American Chemical Society · 2026Article
- Loss of genome maintenance is linked to mTOR complex 1 signaling and accelerates podocyte damage.JCI insight · 2025Article
- Review
- Inhibition of GSK3β is synthetic lethal with FHIT loss in lung cancer by blocking homologous recombination repair.Experimental & molecular medicine · 2025Article
- Article
- Synthesis and Evaluation of 5-(Heteroarylmethylene)hydantoins as Glycogen Synthase Kinase-3β Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Discovery of Novel 4-Hydroxyquinazoline Derivatives: In Silico, In Vivo and In Vitro Studies Using Primary PARPi-Resistant Cell Lines.Molecules (Basel, Switzerland) · 2024Article
- GSK3B inhibition reduced cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- GSK-3α aggravates inflammation, metabolic derangement, and cardiac injury post-ischemia/reperfusion.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance.EMBO molecular medicine · 2023Article
- Repeated treatments of Capan-1 cells with PARP1 and Chk1 inhibitors promote drug resistance, migration and invasion.Cancer biology & therapy · 2022Article
- Precision Medicine forCancers · 2022Review
- β-catenin links cell seeding density to global gene expression during mouse embryonic stem cell differentiation.iScience · 2022Article
- TNKS inhibitors potentiate proliferative inhibition of BET inhibitors via reducing β-Catenin in colorectal cancer cells.American journal of cancer research · 2022Article
- GSK-3β in Pancreatic Cancer: Spotlight on 9-ING-41, Its Therapeutic Potential and Immune Modulatory Properties.Biology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Monotherapy with poly ADP-ribose polymerase (PARP) inhibitors results in a limited objective response rate (≤60% in most cases) in patients with homologous recombination repair (HRR)-deficient cancer, which suggests a high rate of resistance in this subset of patients to PARP inhibitors (PARPi). To overcome resistance to PARPi and to broaden their clinical use, we performed high-throughput screening of 99 anticancer drugs in combination with PARPi to identify potential therapeutic combinations. Here, we found that GSK3 inhibitors (GSK3i) exhibited a strong synergistic effect with PARPi in a panel of colorectal cancer (CRC) cell lines with diverse genetic backgrounds. The combination of GSK3β and PARP inhibition causes replication stress and DNA double-strand breaks, resulting in increased anaphase bridges and abnormal spindles. Mechanistically, inhibition or genetic depletion of GSK3β was found to impair the HRR of DNA and reduce the mRNA and protein level of BRCA1. Finally, we demonstrated that inhibition or depletion of GSK3β could enhance the in vivo sensitivity to simmiparib without toxicity. Our results provide a mechanistic understanding of the combination of PARP and GSK3 inhibition, and support the clinical development of this combination therapy for CRC patients.
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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.