Evidence map›Paper›PMID 33271924›Full record

ArticleCells2020

Revealing Temozolomide Resistance Mechanisms via Genome-Wide CRISPR Libraries.

Clarissa Ribeiro Reily Rocha, Alexandre Reily Rocha, Matheus Molina Silva, Luciana Rodrigues Gomes, Marcela Teatin Latancia, Marina Andrade Tomaz, Izadora de Souza, Linda Karolynne Seregni Monteiro, Carlos Frederico Martins Menck

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.0field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. NRF2 signaling drives chemoresistance in NSCLC and glioblastoma.Molecular and cellular biochemistry · 2026
    Article
  3. Review
  4. Review
  5. The Role of CRISPR and Its Therapeutic Applications in Glioblastoma.International journal of molecular sciences · 2026
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Unlocking Glioblastoma Vulnerabilities with CRISPR-Based Genetic Screening.International journal of molecular sciences · 2024
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Clarissa Ribeiro Reily RochaDepartment of Clinical and Experimental Oncology, Federal University of São Paulo (UNIFESP), São Paulo 04037-003, Brazil.
Alexandre Reily RochaInstitute of Theoretical Physics, State University of São Paulo (UNESP), São Paulo 01140-070, Brazil.ORCID 0000-0001-8874-6947
Matheus Molina SilvaDepartment of Microbiology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-000, Brazil.
Luciana Rodrigues GomesLaboratory of Cell Cycle, Center of Toxins, Immune Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo 05503-001, Brazil.
Marcela Teatin LatanciaDepartment of Microbiology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-000, Brazil.ORCID 0000-0002-3743-7105
Marina Andrade TomazDepartment of Clinical and Experimental Oncology, Federal University of São Paulo (UNIFESP), São Paulo 04037-003, Brazil.
Izadora de SouzaDepartment of Clinical and Experimental Oncology, Federal University of São Paulo (UNIFESP), São Paulo 04037-003, Brazil.
Linda Karolynne Seregni MonteiroDepartment of Clinical and Experimental Oncology, Federal University of São Paulo (UNIFESP), São Paulo 04037-003, Brazil.
Carlos Frederico Martins MenckDepartment of Microbiology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo 05508-000, Brazil.ORCID 0000-0003-1941-0694
Universidade de São Paulo · BRUniversidade Federal de São Paulo · BRInstituto Butantan · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Brain NeoplasmsCell Line, TumorCell SurvivalClustered Regularly Interspaced Short Palindromic RepeatsDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticGenome-Wide Association StudyGlioblastomaHedgehog ProteinsHigh-Throughput Nucleotide SequencingHumansSmall Molecule LibrariesTemozolomideHedgehog ProteinsSmall Molecule LibrariesTemozolomidecancer resistanceCRISPR libraryglioblastomaNRF2temozolomide

Identifiers

PMID33271924
PMCPMC7760831
OpenAlexW3110175203

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.