Evidence map›Paper›PMID 25461627›Full record

ArticlePloS one2014

Specific inhibition of the nuclear exporter exportin-1 attenuates kidney cancer growth.

Hiromi I Wettersten, Yosef Landesman, Sharon Friedlander, Sharon Shacham, Michael Kauffman, Robert H Weiss

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.4field-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

20 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. 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

6 authors at 3 institutions in 1 country.

Hiromi I WetterstenDivision of Nephrology, Dept. of Internal Medicine, University of California Davis, Davis, California, United States of America.
Yosef LandesmanKaryopharm Therapeutics Inc., Natick, Massachusetts, United States of America.
Sharon FriedlanderKaryopharm Therapeutics Inc., Natick, Massachusetts, United States of America.
Sharon ShachamKaryopharm Therapeutics Inc., Natick, Massachusetts, United States of America.
Michael KauffmanKaryopharm Therapeutics Inc., Natick, Massachusetts, United States of America.
Robert H WeissDivision of Nephrology, Dept. of Internal Medicine, University of California Davis, Davis, California, United States of America; Cancer Center, University of California Davis, Davis, California, United States of America; Medical Service, Sacramento VA Medical Center, Sacramento, California, United States of America.
Karyopharm Therapeutics (United States) · USSacramento VA Medical Center · USUniversity of California, Davis · US

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Laura Marcu · 2002 to 2026
$84.9M
SAN ANTONIO CENTER OF BIOMARKERS OF RISK FOR PROSTATE CAU01CA086402 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LEACH, ROBIN JEAN, THOMPSON, IAN M. · 2000 to 2018
$33.1M
Metabolomic discovery and validation of urinary biomarkers for kidney cancerR01CA135401 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI WEISS, ROBERT H. · 2009 to 2013
$1.5M
A Metabolomic Approach to Discovering Biomarkers for ADPKDR01DK082690 · NIDDK · UNIVERSITY OF CALIFORNIA AT DAVIS · PI WEISS, ROBERT H. · 2009 to 2010
$696k
NCI NIH HHS 1R01CA135401-01A1NCI NIH HHS 5U01CA86402NCI NIH HHS P30 CA093373NCI NIH HHS R01 CA135401NCI NIH HHS U01 CA086402NIDDK NIH HHS 1R01DK082690-01A1NIDDK NIH HHS R01 DK082690
6 · The paper itself

Abstract

purposeDespite the advent of FDA-approved therapeutics to a limited number of available targets (kinases and mTOR), PFS of kidney cancer (RCC) has been extended only one to two years due to the development of drug resistance. Here, we evaluate a novel therapeutic for RCC which targets the exportin-1 (XPO1) inhibitor. MATERIALS AND

methodsRCC cells were treated with the orally available XPO1 inhibitor, KPT-330, and cell viability and Annexin V (apoptosis) assays, and cell cycle analyses were performed to evaluate the efficacy of KPT-330 in two RCC cell lines. Immunoblotting and immunofluorescence analysis were performed to validate mechanisms of XPO1 inhibition. The efficacy and on-target effects of KPT-330 were further analyzed in vivo in RCC xenograft mice, and KPT-330-resistant cells were established to evaluate potential mechanisms of KPT-330 resistance.

resultsKPT-330 attenuated RCC viability through growth inhibition and apoptosis induction both in vitro and in vivo, a process in which increased nuclear localization of p21 by XPO1 inhibition played a major role. In addition, KPT-330 resistant cells remained sensitive to the currently approved for RCC multi-kinase inhibitors (sunitinib, sorafenib) and mTOR inhibitors (everolimus, temsirolimus), suggesting that these targeted therapeutics would remain useful as second line therapeutics following KPT-330 treatment.

conclusionThe orally-available XPO1 inhibitor, KPT-330, represents a novel target for RCC whose in vivo efficacy approaches that of sunitinib. In addition, cells resistant to KPT-330 retain their ability to respond to available RCC therapeutics suggesting a novel approach for treatment in KPT-330-naïve as well as -resistant RCC patients.

Indexed as

Active Transport, Cell NucleusAdministration, OralAnimalsApoptosisCarcinoma, Renal CellCell Cycle CheckpointsCell Line, TumorCell NucleusCell ProliferationCell SurvivalCyclin-Dependent Kinase Inhibitor p21Drug ApprovalDrug Resistance, NeoplasmEpithelial CellsExportin 1 ProteinHumansCyclin-Dependent Kinase Inhibitor p21Exportin 1 ProteinHydrazinesKaryopherinsReceptors, Cytoplasmic and NuclearRNA, Small InterferingselinexorTriazoles

Identifiers

PMID25461627
PMCPMC4252068
OpenAlexW2002717016

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.