Evidence map›Paper›PMID 28696296›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression.

Dou Yu, Omar F Khan, Mario L Suvà, Biqin Dong, Wojciech K Panek, Ting Xiao, Meijing Wu, Yu Han, Atique U Ahmed, Irina V Balyasnikova and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
6.5field-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.

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

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

  1. Pooled it
  2. Cancer biology & therapy · 2026
    Article
  3. Potential therapeutic targeting of BKMolecular oncology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Glioblastoma Therapy: Past, Present and Future.International journal of molecular sciences · 2024
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  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

15 authors at 5 institutions in 1 country.

Dou YuDepartment of Neurological Surgery, Brain Tumor Research Institute, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Omar F KhanDepartment of Chemical Engineering, Institute for Medical Engineering and Science, Harvard MIT Division of Health Science and Technology, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Mario L SuvàBroad Institute of Harvard and MIT, Cambridge, MA 02142.
Biqin DongDepartment of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208.
Wojciech K PanekDepartment of Neurological Surgery, Brain Tumor Research Institute, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Ting XiaoDepartment of Neurological Surgery, Brain Tumor Research Institute, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Meijing WuDepartment of Neurological Surgery, Brain Tumor Research Institute, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Yu HanDepartment of Neurological Surgery, Brain Tumor Research Institute, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Atique U AhmedDepartment of Neurological Surgery, Brain Tumor Research Institute, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Irina V BalyasnikovaDepartment of Neurological Surgery, Brain Tumor Research Institute, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Hao F ZhangDepartment of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208.
Cheng SunDepartment of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208.
Robert LangerDepartment of Chemical Engineering, Institute for Medical Engineering and Science, Harvard MIT Division of Health Science and Technology, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Daniel G AndersonDepartment of Chemical Engineering, Institute for Medical Engineering and Science, Harvard MIT Division of Health Science and Technology, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Maciej S LesniakDepartment of Neurological Surgery, Brain Tumor Research Institute, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; maciej.lesniak@northwestern.edu.
Northwestern University · USNeurological Surgery · USMassachusetts Institute of Technology · USCenter for Cancer Research · USMcCormick (United States) · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8M
Therapeutic Targeting of Malignant Glioma Stem CellsR35CA197725 · NCI · UNIVERSITY OF CHICAGO · PI LESNIAK, MACIEJ S · 2015 to 2021
$6.2M
NCATS NIH HHS UL1 TR001422NCI NIH HHS P30 CA060553NCI NIH HHS R35 CA197725
6 · The paper itself

Abstract

Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood-brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting. Recent discoveries in the genetic and epigenetic determinants of BTIC tumorigenesis offer novel opportunities for RNAi-mediated targeting of BTICs. Here we show that BTIC growth arrest in vitro and in vivo is accomplished via concurrent siRNA knockdown of four transcription factors (SOX2, OLIG2, SALL2, and POU3F2) that drive the proneural BTIC phenotype delivered by multiplexed siRNA encapsulation in the lipopolymeric nanoparticle 7C1. Importantly, we demonstrate that 7C1 nano-encapsulation of multiplexed RNAi is a viable BTIC-targeting strategy when delivered directly in vivo in an established mouse brain tumor. Therapeutic potential was most evident via a convection-enhanced delivery method, which shows significant extension of median survival in two patient-derived BTIC xenograft mouse models of GBM. Our study suggests that there is potential advantage in multiplexed targeting strategies for BTICs and establishes a flexible nonviral gene therapy platform with the capacity to channel multiplexed RNAi schemes to address the challenges posed by tumor heterogeneity.

Indexed as

RNA InterferenceAnimalsCarcinogenesisDrug Resistance, NeoplasmFemaleGenetic TherapyGlioblastomaHumansMaleMiceMice, NudeNanoparticlesXenograft Model Antitumor Assaysbrain tumor-initiating cellsconvection-enhanced deliveryglioblastoma transcription factorlipopolymeric nanoparticlesiRNA

Identifiers

PMID28696296
PMCPMC5544292
OpenAlexW2736190544

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.