Evidence map›Paper›PMID 25366336›Full record

ArticleNeuro-oncology2015

Preclinical antitumor efficacy of selective exportin 1 inhibitors in glioblastoma.

Adam L Green, Shakti H Ramkissoon, Dilara McCauley, Kristen Jones, Jennifer A Perry, Jessie Hao-Ru Hsu, Lori A Ramkissoon, Cecile L Maire, Benjamin Hubbell-Engler, David S Knoff and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

63 citing papers in PubMed, 77 citations in OpenAlex.

  1. A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  2. Trial
  3. Review
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  7. Chromenone Derivatives as CRM1 Inhibitors for Targeting Glioblastoma.Chembiochem : a European journal of chemical biology · 2025
    Article
  8. Review
  9. Small-Molecule Drugs in Pediatric Neuro-Oncology.Current oncology (Toronto, Ont.) · 2025
    Review
  10. Article
  11. Article
  12. Phase I Trial of Selinexor in Pediatric Recurrent/Refractory Solid and CNS Tumors (ADVL1414): A Children's Oncology Group Phase I Consortium Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  13. Review
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3 more citing papers are in PubMed but not listed here.

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

13 authors at 7 institutions in 1 country.

Adam L GreenDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Shakti H RamkissoonDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Dilara McCauleyDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Kristen JonesDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Jennifer A PerryDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Jessie Hao-Ru HsuDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Lori A RamkissoonDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Cecile L MaireDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Benjamin Hubbell-EnglerDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
David S KnoffDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Sharon ShachamDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Keith L LigonDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Andrew L KungDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (A.L.G., J.A.P., J.H.-R.H., B.H.-E.); Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts (A.L.G.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (S.H.R., L.A.R., C.L.M., D.S.K., K.L.L.); Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (S.H.R., K.L.L.); Karyopharm Therapeutics, Natick, Massachusetts (D.M., S.S.); Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston, Massachusetts (K.J.); Department of Pathology, Boston Children's Hospital, Boston, Massachusetts (K.L.L.); Department of Pediatrics, Columbia University Medical Center, New York, New York (A.L.K.).
Dana-Farber Cancer Institute · USBoston Children's Hospital · USImaging Center · USBrigham and Women's Hospital · USColumbia University Irving Medical Center · USDana-Farber Brigham Cancer Center · USKaryopharm Therapeutics (United States) · US

Funding

Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI KEITH LLOYD LIGON · 2013 to 2026
$33.5M
Transgenic Mouse and Biobank CoreP01CA095616 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DEPINHO, RONALD ANTHONY · 2003 to 2012
$20.3M
Therapeutic Opportunities for Pediatric AstrocytomaP01CA142536 · NCI · DANA-FARBER CANCER INST · PI SEGAL, ROSALIND A. · 2011 to 2015
$7.9M
ALK signaling in CNS development, ischemic brain injury and gliomagenesisK08NS087118 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI RAMKISSOON, SHAKTI H · 2014 to 2015
$387k
NCI NIH HHS P01 CA095616NCI NIH HHS P01 CA142536NCI NIH HHS P50 CA165962NINDS NIH HHS K08 NS087118
6 · The paper itself

Abstract

backgroundGlioblastoma (GBM) is poorly responsive to current chemotherapy. The nuclear transporter exportin 1 (XPO1, CRM1) is often highly expressed in GBM, which may portend a poor prognosis. Here, we determine the efficacy of novel selective inhibitors of nuclear export (SINE) specific to XPO1 in preclinical models of GBM.

methodsSeven patient-derived GBM lines were treated with 3 SINE compounds (KPT-251, KPT-276, and Selinexor) in neurosphere culture conditions. KPT-276 and Selinexor were also evaluated in a murine orthotopic patient-derived xenograft (PDX) model of GBM. Cell cycle effects were assayed by flow cytometry in vitro and immunohistochemistry in vivo. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase 3/7 activity assays.

resultsTreatment of GBM neurosphere cultures with KPT-276, Selinexor, and KPT-251 revealed dose-responsive growth inhibition in all 7 GBM lines [range of half-maximal inhibitory concentration (IC50), 6-354 nM]. In an orthotopic PDX model, treatment with KPT-276 and Selinexor demonstrated pharmacodynamic efficacy, significantly suppressed tumor growth, and prolonged animal survival. Cellular proliferation was not altered with SINE treatment. Instead, induction of apoptosis was apparent both in vitro and in vivo with SINE treatment, without overt evidence of neurotoxicity.

conclusionsSINE compounds show preclinical efficacy utilizing in vitro and in vivo models of GBM, with induction of apoptosis as the mechanism of action. Selinexor is now in early clinical trials in solid and hematological malignancies. Based on these preclinical data and excellent brain penetration, we have initiated clinical trials of Selinexor in patients with relapsed GBM.

Indexed as

AcrylamidesActive Transport, Cell NucleusAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsCell Cycle CheckpointsCell DifferentiationCell Line, TumorDose-Response Relationship, DrugExportin 1 ProteinGlioblastomaHumansHydrazinesKaryopherinsMacaca fascicularisAcrylamidesAntineoplastic AgentsExportin 1 ProteinHydrazinesKaryopherinsKPT-251KPT-276OxadiazolesReceptors, Cytoplasmic and NuclearselinexorThiazolesTriazolesapoptosisexportin 1glioblastomapatient-derived xenograftSINE

Identifiers

PMID25366336
PMCPMC4482855
OpenAlexW2121229206

What OpenQuestion holds

Textmetadata
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.