Evidence map›Paper›PMID 30652614›Full record

ArticleJCO clinical cancer informatics2018

Leveraging Human Genetics to Guide Cancer Drug Development.

Ben Kinnersley, Amit Sud, Elizabeth A Coker, Joseph E Tym, Patrizio Di Micco, Bissan Al-Lazikani, Richard S Houlston

Abstract read
In one paragraph

Article in JCO clinical cancer informatics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

3 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
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.

Ben KinnersleyAll authors: The Institute of Cancer Research, London, United Kingdom.
Amit SudAll authors: The Institute of Cancer Research, London, United Kingdom.
Elizabeth A CokerAll authors: The Institute of Cancer Research, London, United Kingdom.
Joseph E TymAll authors: The Institute of Cancer Research, London, United Kingdom.
Patrizio Di MiccoAll authors: The Institute of Cancer Research, London, United Kingdom.
Bissan Al-LazikaniAll authors: The Institute of Cancer Research, London, United Kingdom.
Richard S HoulstonAll authors: The Institute of Cancer Research, London, United Kingdom.

Funding

Cancer Research UK 23187
6 · The paper itself

Abstract

purposeThe high attrition rate of cancer drug development programs is a barrier to realizing the promise of precision oncology. We have examined whether the genetic insights from genome-wide association studies of cancer can guide drug development and repurposing in oncology. MATERIALS AND

methodsAcross 37 cancers, we identified 955 genetic risk variants from the National Human Genome Research Institute-European Bioinformatics Institute genome-wide association study catalog. We linked these variants to target genes using strategies that were based on linkage disequilibrium, DNA three-dimensional structure, and integration of predicted gene function and expression. With the use of the Informa Pharmaprojects database, we identified genes that are targets of unique drugs and assessed the level of enrichment that would be afforded by incorporation of genetic information in preclinical and phase II studies. For targets not under development, we implemented machine learning approaches to assess druggability.

resultsFor all preclinical targets incorporating genetic information, a 2.00-fold enrichment of a drug being successfully approved could be achieved (95% CI, 1.14- to 3.48-fold; P = .02). For phase II targets, a 2.75-fold enrichment could be achieved (95% CI, 1.42- to 5.35-fold; P < .001). Application of genetic information suggests potential repurposing of 15 approved nononcology drugs.

conclusionThe findings illustrate the value of using insights from the genetics of inherited cancer susceptibility discovery projects as part of a data-driven strategy to inform drug discovery. Support for cancer germline genetic information for prospective targets is available online from the Institute of Cancer Research.

Indexed as

Drug DevelopmentGenetic Predisposition to DiseaseHumansNeoplasms

Identifiers

PMID30652614
PMCPMC6874034

What OpenQuestion holds

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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.