ArticleCells2020
Revealing Temozolomide Resistance Mechanisms via Genome-Wide CRISPR Libraries.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The trial behind it
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Who cites it
31 citing papers in PubMed, 40 citations in OpenAlex.
- Integrated Genetic Screening Identifies FEN1 as a Selective Vulnerability and Temozolomide Resistance Mediator in Glioblastoma Stem Cells.Cancer research communications · 2026Article
- NRF2 signaling drives chemoresistance in NSCLC and glioblastoma.Molecular and cellular biochemistry · 2026Article
- Decoding and Overcoming Temozolomide Resistance Through CRISPR/Cas Technologies.Molecular diagnosis & therapy · 2026Review
- Systems biology of Wnt signaling in glioma chemotherapy resistance: Integrating multi-omics mechanisms and emerging therapeutic vulnerabilities (Review).Oncology letters · 2026Review
- The Role of CRISPR and Its Therapeutic Applications in Glioblastoma.International journal of molecular sciences · 2026Review
- Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies.International journal of molecular sciences · 2025Review
- Synergistic combination of cannabidiol and celecoxib or 2,5-dimethylcelecoxib exerts oxidative stress-mediated cytotoxicity and mitigates glioblastoma invasiveness.Acta biochimica Polonica · 2025Article
- State of the art CRISPR-based strategies for cancer diagnostics and treatment.Biomarker research · 2024Review
- Metabolic Reprogramming in Glioblastoma Multiforme: A Review of Pathways and Therapeutic Targets.Cells · 2024Review
- Human translesion DNA polymerases ι and κ mediate tolerance to temozolomide in MGMT-deficient glioblastoma cells.DNA repair · 2024Article
- Temozolomide resistance mechanisms: unveiling the role of translesion DNA polymerase kappa in glioblastoma spheroids in vitro.Bioscience reports · 2024Article
- Unlocking Glioblastoma Vulnerabilities with CRISPR-Based Genetic Screening.International journal of molecular sciences · 2024Review
- CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review.Biomedicines · 2024Article
- Mammalian target of rapamycin inhibition protects glioma cells from temozolomide-induced cell death.Cell death discovery · 2024Article
- Chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapy.Molecular and cellular biochemistry · 2023Review
- Temozolomide Resistance in Glioblastoma by NRF2: Protecting the Evil.Biomedicines · 2023Review
- Review
- Genome-wide CRISPR/Cas9 screening for drug resistance in tumors.Frontiers in pharmacology · 2023Review
- Exploring the role of Nrf2 signaling in glioblastoma multiforme.Discover oncology · 2022Review
- Hedgehog signaling regulates the development and treatment of glioblastoma.Oncology letters · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma is a severe type of brain tumor with a poor prognosis and few therapy options. Temozolomide (TMZ) is one of these options, however, with limited success, and failure is mainly due to tumor resistance. In this work, genome-wide CRISPR-Cas9 lentiviral screen libraries for gene knockout or activation were transduced in the human glioblastoma cell line, aiming to identify genes that modulate TMZ resistance. The sgRNAs enriched in both libraries in surviving cells after TMZ treatment were identified by next-generation sequencing (NGS). Pathway analyses of gene candidates on knockout screening revealed several enriched pathways, including the mismatch repair and the Sonic Hedgehog pathways. Silencing three genes ranked on the top 10 list (MSH2, PTCH2, and CLCA2) confirm cell protection from TMZ-induced death. In addition, a CRISPR activation library revealed that NRF2 and Wnt pathways are involved in TMZ resistance. Consistently, overexpression of FZD6, CTNNB1, or NRF2 genes significantly increased cell survival upon TMZ treatment. Moreover, NRF2 and related genes detected in this screen presented a robust negative correlation with glioblastoma patient survival rates. Finally, several gene candidates from knockout or activation screening are targetable by inhibitors or small molecules, and some of them have already been used in the clinic.
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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.