Evidence mapPaperPMID 24401833Full record

Trial reportPharmacogenetics and genomics2014

Pharmacogenomic characterization of gemcitabine response--a framework for data integration to enable personalized medicine.

Michael Harris, Krithika Bhuvaneshwar, Thanemozhi Natarajan, Laura Sheahan, Difei Wang, Mahlet G Tadesse, Ira Shoulson, Ross Filice, Kenneth Steadman, Michael J Pishvaian and 2 more

Erratum issuedOpen access · greenAbstract readClinical Trial, Phase III
In one paragraph

Trial report in Pharmacogenetics and genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Observational
  5. Article
  6. Article
  7. Oncotarget · 2018
    Article
  8. Article
  9. Article
  10. Review
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

12 authors at 5 institutions in 1 country.

Michael HarrisaInnovation Center for Biomedical Informatics bLombardi Comprehensive Cancer Center, Developmental Therapeutics Program cDepartment of Neurology, Georgetown University Medical Center dDepartment of Mathematics and Statistics, Georgetown University, Washington, District of Columbia eESAC Inc., Rockville fUS Food and Drug Administration, Silver Spring, Maryland, USA.
Krithika Bhuvaneshwar
Thanemozhi Natarajan
Laura Sheahan
Difei Wang
Mahlet G Tadesse
Ira Shoulson
Ross Filice
Kenneth Steadman
Michael J Pishvaian
Subha Madhavan
John Deeken
Vince Lombardi Cancer Clinic · USGeorgetown University · USEnterprise Science and Computing (United States) · USGeorgetown University Medical Center · USUnited States Food and Drug Administration · US

Funding

Tissue Culture and Biobanking Shared ResourceP30CA051008 · GEORGETOWN UNIVERSITY · 1990 to 2025
$20.3M
FDA HHS U01 FD004319NCI NIH HHS P30 CA051008NCI NIH HHS P30CA051008NCI NIH HHS U54 CA149147
6 · The paper itself

Abstract

objectivesResponse to the oncology drug gemcitabine may be variable in part due to genetic differences in the enzymes and transporters responsible for its metabolism and disposition. The aim of our in-silico study was to identify gene variants significantly associated with gemcitabine response that may help to personalize treatment in the clinic.

methodsWe analyzed two independent data sets: (a) genotype data from NCI-60 cell lines using the Affymetrix DMET 1.0 platform combined with gemcitabine cytotoxicity data in those cell lines, and (b) genome-wide association studies (GWAS) data from 351 pancreatic cancer patients treated on an NCI-sponsored phase III clinical trial. We also performed a subset analysis on the GWAS data set for 135 patients who were given gemcitabine+placebo. Statistical and systems biology analyses were performed on each individual data set to identify biomarkers significantly associated with gemcitabine response.

resultsGenetic variants in the ABC transporters (ABCC1, ABCC4) and the CYP4 family members CYP4F8 and CYP4F12, CHST3, and PPARD were found to be significant in both the NCI-60 and GWAS data sets. We report significant association between drug response and variants within members of the chondroitin sulfotransferase family (CHST) whose role in gemcitabine response is yet to be delineated.

conclusionBiomarkers identified in this integrative analysis may contribute insights into gemcitabine response variability. As genotype data become more readily available, similar studies can be conducted to gain insights into drug response mechanisms and to facilitate clinical trial design and regulatory reviews.

Indexed as

Antimetabolites, AntineoplasticATP-Binding Cassette TransportersCell Line, TumorDeoxycytidineGemcitabineGene Expression Regulation, NeoplasticGenetic MarkersGenetic VariationGenome-Wide Association StudyGenotypeHumansLinkage DisequilibriumPancreatic NeoplasmsPharmacogeneticsPolymorphism, Single NucleotidePrecision MedicineAntimetabolites, AntineoplasticATP-Binding Cassette TransportersDeoxycytidineGemcitabineGenetic MarkersSulfotransferases

Identifiers

PMID24401833
PMCPMC3888473
OpenAlexW2020018956

What Socratic 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 Socratic graph.