Evidence map›Paper›PMID 27893412›Full record

ArticleOncotarget2017

Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma.

Manoj Garg, Deepika Kanojia, Anand Mayakonda, Jonathan W Said, Ngan B Doan, Wenwen Chien, Trivadi S Ganesan, Linda Shyue Huey Chuang, Nachiyappan Venkatachalam, Erkan Baloglu and 3 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

36 citing papers in PubMed, 65 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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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 5 institutions in 3 countries.

Manoj GargCancer Science Institute (CSI) of Singapore, National University of Singapore, Singapore.
Deepika KanojiaCancer Science Institute (CSI) of Singapore, National University of Singapore, Singapore.
Anand MayakondaCancer Science Institute (CSI) of Singapore, National University of Singapore, Singapore.
Jonathan W SaidDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, Los Angeles, CA, USA.
Ngan B DoanDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, Los Angeles, CA, USA.
Wenwen ChienCancer Science Institute (CSI) of Singapore, National University of Singapore, Singapore.
Trivadi S GanesanDepartment of Medical Oncology and Clinical Research, Cancer Institute (WIA), Adyar Chennai, India.
Linda Shyue Huey ChuangCancer Science Institute (CSI) of Singapore, National University of Singapore, Singapore.
Nachiyappan VenkatachalamCancer Science Institute (CSI) of Singapore, National University of Singapore, Singapore.
Erkan BalogluKaryopharm Therapeutics Inc, Newton, MA, USA.
Sharon ShachamKaryopharm Therapeutics Inc, Newton, MA, USA.
Michael KauffmanKaryopharm Therapeutics Inc, Newton, MA, USA.
H Phillip KoefflerCancer Science Institute (CSI) of Singapore, National University of Singapore, Singapore.
National University of Singapore · SGKaryopharm Therapeutics (United States) · USCancer Institute (WIA) · INNational University Cancer Institute, Singapore · SGUniversity of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Exportin-1 mediates nuclear export of multiple tumor suppressor and growth regulatory proteins. Aberrant expression of exportin-1 is noted in human malignancies, resulting in cytoplasmic mislocalization of its target proteins. We investigated the efficacy of selinexor against liposarcoma cells both in vitro and in vivo. Exportin-1 was highly expressed in liposarcoma samples and cell lines as determined by immunohistochemistry, western blot, and immunofluorescence assay. Knockdown of endogenous exportin-1 inhibited proliferation of liposarcoma cells. Selinexor also significantly decreased cell proliferation as well as induced cell cycle arrest and apoptosis of liposarcoma cells. The drug also significantly decreased tumor volumes and weights of liposarcoma xenografts. Importantly, selinexor inhibited insulin-like growth factor 1 (IGF1) activation of IGF-1R/AKT pathway through upregulation of insulin-like growth factor binding protein 5 (IGFBP5). Further, overexpression and knockdown experiments showed that IGFBP5 acts as a tumor suppressor and its expression was restored upon selinexor treatment of liposarcoma cells. Selinexor decreased aurora kinase A and B levels in these cells and inhibitors of these kinases suppressed the growth of the liposarcoma cells. Overall, our study showed that selinexor treatment restored tumor suppressive function of IGFBP5 and inhibited aurora kinase A and B in liposarcoma cells supporting the usefulness of selinexor as a potential therapeutic strategy for the treatment of this cancer.

Indexed as

AnimalsAntineoplastic AgentsApoptosisAurora Kinase AAurora Kinase BCell Cycle CheckpointsCell Line, TumorCell ProliferationDose-Response Relationship, DrugExportin 1 ProteinGene Expression Regulation, NeoplasticHumansHydrazinesInsulin-Like Growth Factor Binding Protein 5KaryopherinsLiposarcomaAntineoplastic AgentsAURKA protein, humanAURKB protein, humanAurora Kinase AAurora Kinase BExportin 1 ProteinHydrazinesIGF1R protein, humanInsulin-Like Growth Factor Binding Protein 5KaryopherinsProto-Oncogene Proteins c-aktReceptor, IGF Type 1Receptors, Cytoplasmic and NuclearReceptors, SomatomedinselinexorTriazolescell cycleIGFBP5selinexorxenograft

Identifiers

PMID27893412
PMCPMC5352339
OpenAlexW2553418614

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.