Evidence map›Paper›PMID 31303577›Full record

ArticleCell chemical biology2019

Engineering Forward Genetics into Cultured Cancer Cells for Chemical Target Identification.

Juan Manuel Povedano, Joel Liou, David Wei, Ashwin Srivatsav, Jiwoong Kim, Yang Xie, Deepak Nijhawan, David G McFadden

Open access · bronzeAbstract read
In one paragraph

Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

12 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Exploring ovarian cancer cell resistance to rhenium anticancer complexes.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2020
    Article
  10. Exploring Ovarian Cancer Cell Resistance to Rhenium Anticancer Complexes.Angewandte Chemie (International ed. in English) · 2020
    Article
  11. Review
  12. Review
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

8 authors at 2 institutions in 1 country.

Juan Manuel PovedanoDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Joel LiouDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
David WeiDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Ashwin SrivatsavDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jiwoong KimDepartment of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Yang XieDepartment of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Deepak NijhawanDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
David G McFaddenDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: david.mcfadden@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USSouthwestern Medical Center · US

Funding

Understanding the mechanism of action for anticancer sulfonamides that target splicingR37CA226771 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI NIJHAWAN, DEEPAK · 2018 to 2024
$2.8M
Tumor-targeted inhibitors of stearoyl-CoA desaturase for the treatment of cancer.R01CA217333 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI NIJHAWAN, DEEPAK · 2018 to 2022
$2.7M
NCI NIH HHS R01 CA217333NCI NIH HHS R37 CA226771
6 · The paper itself

Abstract

Target identification for biologically active small molecules remains a major barrier for drug discovery. Cancer cells exhibiting defective DNA mismatch repair (dMMR) have been used as a forward genetics system to uncover compound targets. However, this approach has been limited by the dearth of cancer cell lines that harbor naturally arising dMMR. Here, we establish a platform for forward genetic screening using CRISPR/Cas9 to engineer dMMR into mammalian cells. We demonstrate the utility of this approach to identify mechanisms of drug action in mouse and human cancer cell lines using in vitro selections against three cellular toxins. In each screen, compound-resistant alleles emerged in drug-resistant clones, supporting the notion that engineered dMMR enables forward genetic screening in mammalian cells.

Indexed as

AnimalsCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsDNA Mismatch RepairDrug DiscoveryGenetic EngineeringGenetic TestingHumansMiceNeoplasmsEwing sarcomaforward geneticsgenetically-engineered mouse model (GEMM)hypermutationmismatch repairmismatch repair deficiencyphenotypic screeningtarget identification

Identifiers

PMID31303577
PMCPMC6866228
OpenAlexW2961278528

What OpenQuestion holds

Textmetadata
LicenceTDM
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.