Evidence map›Paper›PMID 26918731›Full record

ArticleOncotarget2016

Preclinical activity of selinexor, an inhibitor of XPO1, in sarcoma.

Robert Nakayama, Yi-Xiang Zhang, Jeffrey T Czaplinski, Alex J Anatone, Ewa T Sicinska, Jonathan A Fletcher, George D Demetri, Andrew J Wagner

Registry-linked trialOpen access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06114004 (Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcomas), which is not on this map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
7.9field-weighted citation impact, top 2% 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.

NCT06114004 phase2recruitingnot on this mapstarted 2023, after this paper: background citation

Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcomas

TypeinterventionalSponsorAsociación Europea y Latinoamericana SELNET para la Investigación en SarcomasRan2023 to 2026Enrolled88ConditionsSarcoma,Soft TissueArmsSelinexor 20 MG, Gemcitabine
3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 72 citations in OpenAlex.

  1. Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022
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  3. Phase IB Study of Selinexor, a First-in-Class Inhibitor of Nuclear Export, in Patients With Advanced Refractory Bone or Soft Tissue Sarcoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016
    Trial
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Robert NakayamaLudwig Center at Dana-Farber/Harvard and Center for Sarcoma and Bone Oncology, Department of Medical Oncology, Harvard Medical School, Boston, MA, USA.
Yi-Xiang ZhangLudwig Center at Dana-Farber/Harvard and Center for Sarcoma and Bone Oncology, Department of Medical Oncology, Harvard Medical School, Boston, MA, USA.
Jeffrey T CzaplinskiDepartment of Medical Oncology and Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Alex J AnatoneDepartment of Medical Oncology and Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Ewa T SicinskaDepartment of Medical Oncology and Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Jonathan A FletcherDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
George D DemetriLudwig Center at Dana-Farber/Harvard and Center for Sarcoma and Bone Oncology, Department of Medical Oncology, Harvard Medical School, Boston, MA, USA.
Andrew J WagnerLudwig Center at Dana-Farber/Harvard and Center for Sarcoma and Bone Oncology, Department of Medical Oncology, Harvard Medical School, Boston, MA, USA.
Harvard University · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · US

Funding

Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2M
Tissue and Pathology ResourcesU54CA168512 · NCI · SARC · PI BAKER, LAURENCE HOWARD, POLLOCK, RAPHAEL E. · 2012 to 2016
$11.0M
NCI NIH HHS P50 CA127003NCI NIH HHS U54 CA168512
6 · The paper itself

Abstract

Selinexor is an orally bioavailable selective inhibitor of nuclear export that has been demonstrated to have preclinical activity in various cancer types and that is currently in Phase I and II clinical trials for advanced cancers. In this study, we evaluated the effects of selinexor in several preclinical models of various sarcoma subtypes. The efficacy of selinexor was investigated in vitro and in vivo using 17 cell lines and 9 sarcoma xenograft models including gastrointestinal stromal tumor (GIST), liposarcoma (LPS), leiomyosarcoma, rhabdomyosarcoma, undifferentiated sarcomas, and alveolar soft part sarcoma (ASPS). Most sarcoma cell lines were sensitive to selinexor with IC50s ranging from 28.8 nM to 218.2 nM (median: 66.1 nM). Selinexor suppressed sarcoma tumor xenograft growth, including models of ASPS that were resistant in vitro. In GIST cells with KIT mutations, selinexor induced G1- arrest without attenuation of phosphorylation of KIT, AKT, or MAPK, in contrast to imatinib. In LPS cell lines with MDM2 and CDK4 amplification, selinexor induced G1-arrest and apoptosis irrespective of p53 expression or mutation and irrespective of RB expression. Selinexor increased p53 and p21 expression at the protein but not RNA level, indicating a post-transcriptional effect. These results indicate that selinexor has potent in vitro and in vivo activity against a wide variety of sarcoma models by inducing G1-arrest independent of known molecular mechanisms in GIST and LPS. These studies further justify the exploration of selinexor in clinical trials targeting various sarcoma subtypes.

Indexed as

AnimalsApoptosisBlotting, WesternCell Line, TumorCell SurvivalDose-Response Relationship, DrugDrug Screening Assays, AntitumorExportin 1 ProteinFemaleG1 Phase Cell Cycle CheckpointsHumansHydrazinesKaryopherinsMice, NudeProto-Oncogene Proteins c-kitReceptors, Cytoplasmic and NuclearExportin 1 ProteinHydrazinesKaryopherinsProto-Oncogene Proteins c-kitReceptors, Cytoplasmic and NuclearselinexorTriazolesgastrointestinal stromal tumorliposarcomapreclinical studysarcomaselinexor

Identifiers

PMID26918731
PMCPMC4941336
OpenAlexW2320896036

What OpenQuestion holds

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Registered trials

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.