Evidence map›Paper›PMID 37917583›Full record

ArticleCell reports2023

Targeting the non-coding genome and temozolomide signature enables CRISPR-mediated glioma oncolysis.

I-Li Tan, Alexendar R Perez, Rachel J Lew, Xiaoyu Sun, Alisha Baldwin, Yong K Zhu, Mihir M Shah, Mitchel S Berger, Jennifer A Doudna, Christof Fellmann

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 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

10 authors at 2 institutions in 1 country.

I-Li TanGladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Alexendar R PerezDepartment of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94131, USA; Silico Therapeutics, San Francisco, CA 94131, USA.
Rachel J LewGladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA.
Xiaoyu SunSilico Therapeutics, San Francisco, CA 94131, USA.
Alisha BaldwinGladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Yong K ZhuGladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Mihir M ShahGladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Mitchel S BergerDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94131, USA.
Jennifer A DoudnaGladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Christof FellmannGladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: christof.fellmann@gladstone.ucsf.edu.
Gladstone Institutes · USUniversity of California, San Francisco · US

Funding

Mechanism and Therapeutic Application of RNA-Guided Immune SystemsR00GM118909 · NIGMS · J. DAVID GLADSTONE INSTITUTES · PI FELLMANN, CHRISTOF · 2018 to 2020
$747k
Mapping cellular communication at single-cell resolution through novel CRISPR systemsR35GM143124 · NIGMS · J. DAVID GLADSTONE INSTITUTES · PI FELLMANN, CHRISTOF · 2021 to 2021
$473k
Mechanism and therapeutic application of RNA-guided immune systemsK99GM118909 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI FELLMANN, CHRISTOF · 2016 to 2017
$180k
Howard Hughes Medical InstituteNIGMS NIH HHS K99 GM118909NIGMS NIH HHS R00 GM118909NIGMS NIH HHS R35 GM143124
6 · The paper itself

Abstract

Glioblastoma (GBM) is the most common lethal primary brain cancer in adults. Despite treatment regimens including surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy, growth of residual tumor leads to therapy resistance and death. At recurrence, a quarter to a third of all gliomas have hypermutated genomes, with mutational burdens orders of magnitude greater than in normal tissue. Here, we quantified the mutational landscape progression in a patient's primary and recurrent GBM, and we uncovered Cas9-targetable repeat elements. We show that CRISPR-mediated targeting of highly repetitive loci enables rapid elimination of GBM cells, an approach we term "genome shredding." Importantly, in the patient's recurrent GBM, we identified unique repeat sequences with TMZ mutational signature and demonstrated that their CRISPR targeting enables cancer-specific cell ablation. "Cancer shredding" leverages the non-coding genome and therapy-induced mutational signatures for targeted GBM cell depletion and provides an innovative paradigm to develop treatments for hypermutated glioma.

Indexed as

Brain NeoplasmsGlioblastomaGliomaAntineoplastic Agents, AlkylatingCell Line, TumorDrug Resistance, NeoplasmHumansNeoplasm Recurrence, LocalTemozolomideAntineoplastic Agents, AlkylatingTemozolomidecancer shreddingCP: CancerCRISPR-Cas9genome shreddingglioblastomahypermutated glioma

Identifiers

PMID37917583
PMCPMC10725516
OpenAlexW4388231537

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.