Evidence map›Paper›PMID 31113993›Full record

ArticleScientific reports2019

Genome-scale CRISPR/Cas9 screen determines factors modulating sensitivity to ProTide NUC-1031.

Awa Sarr, Jennifer Bré, In Hwa Um, Tsz Huen Chan, Peter Mullen, David J Harrison, Paul A Reynolds

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance MechanismsClinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  7. Review
  8. Review
  9. Review
  10. Chemoresistance in Pancreatic Cancer.International journal of molecular sciences · 2019
    Review
  11. CRISPR Cas9 in Pancreatic Cancer Research.Frontiers in cell and developmental biology · 2019
    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

7 authors at 1 institution in 1 country.

Awa SarrSchool of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK.
Jennifer BréSchool of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK.
In Hwa UmSchool of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK.
Tsz Huen ChanSchool of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK.
Peter MullenSchool of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK.
David J HarrisonSchool of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK.ORCID http://orcid.org/0000-0001-9041-9988
Paul A ReynoldsSchool of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK. par10@st-andrews.ac.uk.ORCID http://orcid.org/0000-0001-8738-1245
University of St Andrews · GB

Funding

Biotechnology and Biological Sciences Research Council BB/J004243/1Medical Research Council MR/K001744/1
6 · The paper itself

Abstract

Gemcitabine is a fluoropyrimidine analogue that is used as a mainstay of chemotherapy treatment for pancreatic and ovarian cancers, amongst others. Despite its widespread use, gemcitabine achieves responses in less than 10% of patients with metastatic pancreatic cancer and has a very limited impact on overall survival due to intrinsic and acquired resistance. NUC-1031 (Acelarin), a phosphoramidate transformation of gemcitabine, was the first anti-cancer ProTide to enter the clinic. We find it displays important in vitro cytotoxicity differences to gemcitabine, and a genome-wide CRISPR/Cas9 genetic screening approach identified only the pyrimidine metabolism pathway as modifying cancer cell sensitivity to NUC-1031. Low deoxycytidine kinase expression in tumour biopsies from patients treated with gemcitabine, assessed by immunostaining and image analysis, correlates with a poor prognosis, but there is no such correlation in tumour biopsies from a Phase I cohort treated with NUC-1031.

Indexed as

Antineoplastic AgentsBiomarkers, TumorClinical Trials, Phase I as TopicCRISPR-Cas SystemsCytidine MonophosphateDeoxycytidineDeoxycytidine KinaseDrug Resistance, NeoplasmFemaleGemcitabineHEK293 CellsHumansOvarian NeoplasmsPancreatic NeoplasmsAntineoplastic AgentsBiomarkers, TumorCytidine MonophosphateDeoxycytidineDeoxycytidine KinaseGemcitabineNUC-1031

Identifiers

PMID31113993
PMCPMC6529431
OpenAlexW2946210668

What OpenQuestion holds

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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.