Evidence map›Paper›PMID 30871186›Full record

ArticleCancers2019

Exploring the Frequency of Homologous Recombination DNA Repair Dysfunction in Multiple Cancer Types.

Lucy Gentles, Bojidar Goranov, Elizabeth Matheson, Ashleigh Herriott, Angelika Kaufmann, Sally Hall, Asima Mukhopadhyay, Yvette Drew, Nicola J Curtin, Rachel L O'Donnell

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 19% 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, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. PARP Inhibitors Display Differential Efficacy in Models ofInternational journal of molecular sciences · 2021
    Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. 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

10 authors at 4 institutions in 2 countries.

Lucy GentlesNorthern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. lucy.gentles@ncl.ac.uk.
Bojidar GoranovNorthern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. bojidar@doctors.org.uk.
Elizabeth MathesonNorthern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. lizmatheson1@gmail.com.
Ashleigh HerriottNorthern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Ashleighjherriott1@gmail.com.
Angelika KaufmannNorthern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. angelikakaufmann@gmx.net.
Sally HallNorthern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Sally.Hall@newcastle.ac.uk.
Asima MukhopadhyayNorthern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. asima7@yahoo.co.in.
Yvette DrewNorthern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. yvette.drew@ncl.ac.uk.ORCID 0000-0001-6676-9224
Nicola J CurtinNorthern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. nicola.curtin@ncl.ac.uk.
Rachel L O'DonnellNorthern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. rachel.o'donnell@ncl.ac.uk.
Newcastle University · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GBQueen Elizabeth Hospital · GBTata Medical Center · IN

Funding

Newcastle Healthcare Charity JAG/ML/0614
6 · The paper itself

Abstract

Dysfunctional homologous recombination DNA repair (HRR), frequently due to BRCA mutations, is a determinant of sensitivity to platinum chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi). In cultures of ovarian cancer cells, we have previously shown that HRR function, based upon RAD51 foci quantification, correlated with growth inhibition ex vivo induced by rucaparib (a PARPi) and 12-month survival following platinum chemotherapy. The aim of this study was to determine the feasibility of measuring HRR dysfunction (HRD) in other tumours, in order to estimate the frequency and hence wider potential of PARPi. A total of 24 cultures were established from ascites sampled from 27 patients with colorectal, upper gastrointestinal, pancreatic, hepatobiliary, breast, mesothelioma, and non-epithelial ovarian cancers; 8 were HRD. Cell growth following continuous exposure to 10 μM of rucaparib was lower in HRD cultures compared to HRR-competent (HRC) cultures. Overall survival in the 10 patients who received platinum-based therapy was marginally higher in the 3 with HRD ascites (median overall survival of 17 months, range 10 to 90) compared to the 7 patients with HRC ascites (nine months, range 1 to 55). HRR functional assessment in primary cultures, from several tumour types, revealed that a third are HRD, justifying the further exploration of PARPi therapy in a broader range of tumours.

Indexed as

functional biomarker assayhomologous recombination DNA repairplatinum-based chemotherapypoly(ADP-ribose) polymerase inhibitors (PARPi), primary cultureprecision medicine

Identifiers

PMID30871186
PMCPMC6468835
OpenAlexW2920950886

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.