Evidence map›Paper›PMID 25605818›Full record

ArticleNeuro-oncology2015

In vitro screen of a small molecule inhibitor drug library identifies multiple compounds that synergize with oncolytic myxoma virus against human brain tumor-initiating cells.

Brienne A McKenzie, Franz J Zemp, Alexandra Pisklakova, Aru Narendran, Grant McFadden, Xueqing Lun, Rajappa S Kenchappa, Ebba U Kurz, Peter A Forsyth

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
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 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

21 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Oncolytic Viruses as a Platform for the Treatment of Malignant Brain Tumors.International journal of molecular sciences · 2020
    Review
  5. Review
  6. Review
  7. Oncolytic Virotherapy with Myxoma Virus.Journal of clinical medicine · 2020
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Combinatorial Effects of VEGFR Kinase Inhibitor Axitinib and Oncolytic Virotherapy in Mouse and Human Glioblastoma Stem-Like Cell Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Oncolytic virotherapy for urological cancers.Nature reviews. Urology · 2016
    Review
  19. Review
  20. Article
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

9 authors at 3 institutions in 2 countries.

Brienne A McKenzieSouthern Alberta Cancer Research Institute, University of Calgary, Calgary, Canada (B.A.M., F.J.Z., A.N., X.L, E.U.K, P.A.F.); Department of Pediatrics, University of Calgary, Calgary, Canada (A.N.); Department of Oncology, University of Calgary, Calgary, Canada (A.N., P.A.F.); Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada (E.U.K.); Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K, P.A.F.); Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida (G.M.).
Franz J ZempSouthern Alberta Cancer Research Institute, University of Calgary, Calgary, Canada (B.A.M., F.J.Z., A.N., X.L, E.U.K, P.A.F.); Department of Pediatrics, University of Calgary, Calgary, Canada (A.N.); Department of Oncology, University of Calgary, Calgary, Canada (A.N., P.A.F.); Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada (E.U.K.); Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K, P.A.F.); Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida (G.M.).
Alexandra PisklakovaSouthern Alberta Cancer Research Institute, University of Calgary, Calgary, Canada (B.A.M., F.J.Z., A.N., X.L, E.U.K, P.A.F.); Department of Pediatrics, University of Calgary, Calgary, Canada (A.N.); Department of Oncology, University of Calgary, Calgary, Canada (A.N., P.A.F.); Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada (E.U.K.); Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K, P.A.F.); Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida (G.M.).
Aru NarendranSouthern Alberta Cancer Research Institute, University of Calgary, Calgary, Canada (B.A.M., F.J.Z., A.N., X.L, E.U.K, P.A.F.); Department of Pediatrics, University of Calgary, Calgary, Canada (A.N.); Department of Oncology, University of Calgary, Calgary, Canada (A.N., P.A.F.); Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada (E.U.K.); Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K, P.A.F.); Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida (G.M.).
Grant McFaddenSouthern Alberta Cancer Research Institute, University of Calgary, Calgary, Canada (B.A.M., F.J.Z., A.N., X.L, E.U.K, P.A.F.); Department of Pediatrics, University of Calgary, Calgary, Canada (A.N.); Department of Oncology, University of Calgary, Calgary, Canada (A.N., P.A.F.); Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada (E.U.K.); Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K, P.A.F.); Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida (G.M.).
Xueqing LunSouthern Alberta Cancer Research Institute, University of Calgary, Calgary, Canada (B.A.M., F.J.Z., A.N., X.L, E.U.K, P.A.F.); Department of Pediatrics, University of Calgary, Calgary, Canada (A.N.); Department of Oncology, University of Calgary, Calgary, Canada (A.N., P.A.F.); Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada (E.U.K.); Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K, P.A.F.); Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida (G.M.).
Rajappa S KenchappaSouthern Alberta Cancer Research Institute, University of Calgary, Calgary, Canada (B.A.M., F.J.Z., A.N., X.L, E.U.K, P.A.F.); Department of Pediatrics, University of Calgary, Calgary, Canada (A.N.); Department of Oncology, University of Calgary, Calgary, Canada (A.N., P.A.F.); Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada (E.U.K.); Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K, P.A.F.); Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida (G.M.).
Ebba U KurzSouthern Alberta Cancer Research Institute, University of Calgary, Calgary, Canada (B.A.M., F.J.Z., A.N., X.L, E.U.K, P.A.F.); Department of Pediatrics, University of Calgary, Calgary, Canada (A.N.); Department of Oncology, University of Calgary, Calgary, Canada (A.N., P.A.F.); Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada (E.U.K.); Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K, P.A.F.); Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida (G.M.).
Peter A ForsythSouthern Alberta Cancer Research Institute, University of Calgary, Calgary, Canada (B.A.M., F.J.Z., A.N., X.L, E.U.K, P.A.F.); Department of Pediatrics, University of Calgary, Calgary, Canada (A.N.); Department of Oncology, University of Calgary, Calgary, Canada (A.N., P.A.F.); Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada (E.U.K.); Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K, P.A.F.); Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, Florida (G.M.).
Moffitt Cancer Center · USUniversity of Calgary · CAUniversity of Florida · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
Studies in Poxvirus Host Range Genes and TropismR01AI080607 · NIAID · UNIVERSITY OF FLORIDA · PI RAHMAN, MASMUDUR MOHAMMED · 2009 to 2025
$5.6M
Integrative Molecular Epidemiology WorkshopR25CA174664 · NCI · AMERICAN ASSOCIATION FOR CANCER RESEARCH · PI Shelley S Tworoger · 2013 to 2026
$2.8M
Manipulation of inflammasomes and NF-kB signaling in human myeloid cells by MyxomR01AI100987 · NIAID · UNIVERSITY OF FLORIDA · PI MCFADDEN, GRANT · 2013 to 2017
$1.9M
Myxoma Virus (MV) Oncolysis for treating human cancerR01CA138541 · NCI · UNIVERSITY OF FLORIDA · PI MCFADDEN, GRANT · 2010 to 2014
$1.5M
Canadian Institutes of Health ResearchNCI NIH HHS P30 CA076292NCI NIH HHS R01 CA138541NCI NIH HHS R25 CA174664NIAID NIH HHS R01 AI080607NIAID NIH HHS R01 AI100987
6 · The paper itself

Abstract

backgroundBrain tumor-initiating cells (BTICs) are stem-like cells hypothesized to form a disease reservoir that mediates tumor recurrence in high-grade gliomas. Oncolytic virotherapy uses replication-competent viruses to target and kill malignant cells and has been evaluated in clinic for glioma therapy with limited results. Myxoma virus (MyxV) is a safe and highly effective oncolytic virus (OV) in conventional glioma models but, as seen with other OVs, is only modestly effective for patient-derived BTICs. The objective of this study was to determine whether MyxV treatment against human BTICs could be improved by combining chemotherapeutics and virotherapy.

methodsA 73-compound library of drug candidates in clinical use or preclinical development was screened to identify compounds that sensitize human BTICs to MyxV treatment in vitro, and synergy was evaluated mathematically in lead compounds using Chou-Talalay analyses. The effects of combination therapy on viral gene expression and viral replication were also assessed.

resultsEleven compounds that enhance MyxV efficacy were identified, and 6 were shown to synergize with the virus using Chou-Talalay analyses. Four of the synergistic compounds were shown to significantly increase viral gene expression, indicating a potential mechanism for synergy. Three highly synergistic compounds (axitinib, a VEGFR inhibitor; rofecoxib, a cyclooxygenase-2 inhibitor; and pemetrexed, a folate anti-metabolite) belong to classes of compounds that have not been previously shown to synergize with oncolytic viruses in vitro.

conclusionsThis study has identified multiple novel drug candidates that synergistically improve MyxV efficacy in a preclinical BTIC glioma model.

Indexed as

Oncolytic VirotherapyAntineoplastic AgentsAxitinibBrain NeoplasmsCell Line, TumorCombined Modality TherapyGlioblastomaHumansImidazolesIndazolesIn Vitro TechniquesMyxoma virusNeoplastic Stem CellsOncolytic VirusesSmall Molecule LibrariesAntineoplastic AgentsAxitinibImidazolesIndazolesSmall Molecule Librariesbrain tumor-initiating cellsmyxoma virusoncolytic virotherapysynergy

Identifiers

PMID25605818
PMCPMC4490869
OpenAlexW2125940163

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.