Evidence map›Paper›PMID 35802645›Full record

ArticleCancer research2022

Efficient Correction of Oncogenic KRAS and TP53 Mutations through CRISPR Base Editing.

Shady Sayed, Olga A Sidorova, Alexander Hennig, Martina Augsburg, Catherine P Cortés Vesga, Moustafa Abohawya, Lukas T Schmitt, Duran Sürün, Daniel E Stange, Jovan Mircetic and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 38 citations in OpenAlex.

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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

11 authors at 3 institutions in 1 country.

Shady SayedMedical Systems Biology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0002-3209-238X
Olga A SidorovaMedical Systems Biology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Alexander HennigNational Center for Tumor Diseases (NCT), Dresden, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
Martina AugsburgMedical Systems Biology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0003-4818-2192
Catherine P Cortés VesgaMedical Systems Biology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0001-5479-932X
Moustafa AbohawyaGerman Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) Partner Site, Dresden, Germany.ORCID 0000-0003-0959-1954
Lukas T SchmittMedical Systems Biology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0002-5455-4901
Duran SürünMedical Systems Biology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Daniel E StangeNational Center for Tumor Diseases (NCT), Dresden, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.ORCID 0000-0003-4246-2230
Jovan MirceticMedical Systems Biology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0002-9481-240X
Frank BuchholzMedical Systems Biology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0002-4577-3344
University Hospital Carl Gustav Carus · DEGerman Cancer Research Center · DEHelmholtz-Zentrum Dresden-Rossendorf · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

KRAS is the most frequently mutated oncogene in human cancer, and its activating mutations represent long-sought therapeutic targets. Programmable nucleases, particularly the CRISPR-Cas9 system, provide an attractive tool for genetically targeting KRAS mutations in cancer cells. Here, we show that cleavage of a panel of KRAS driver mutations suppresses growth in various human cancer cell lines, revealing their dependence on mutant KRAS. However, analysis of the remaining cell population after long-term Cas9 expression unmasked the occurence of oncogenic KRAS escape variants that were resistant to Cas9-cleavage. In contrast, the use of an adenine base editor to correct oncogenic KRAS mutations progressively depleted the targeted cells without the appearance of escape variants and allowed efficient and simultaneous correction of a cancer-associated TP53 mutation. Oncogenic KRAS and TP53 base editing was possible in patient-derived cancer organoids, suggesting that base editor approaches to correct oncogenic mutations could be developed for functional interrogation of vulnerabilities in a personalized manner for future precision oncology applications. SIGNIFICANCE: Repairing KRAS mutations with base editors can be used for providing a better understanding of RAS biology and may lay the foundation for improved treatments for KRAS-mutant cancers.

Indexed as

NeoplasmsProto-Oncogene Proteins p21(ras)CarcinogenesisCRISPR-Cas SystemsGene EditingHumansMutationOncogenesPrecision MedicineTumor Suppressor Protein p53KRAS protein, humanProto-Oncogene Proteins p21(ras)TP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID35802645
PMCPMC9437569
OpenAlexW4284967611

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.