Evidence map›Paper›PMID 30622322›Full record

ArticleCancer gene therapy2019

JAK/STAT inhibition with ruxolitinib enhances oncolytic virotherapy in non-small cell lung cancer models.

Manish R Patel, Alexander Dash, Blake A Jacobson, Yan Ji, Daniel Baumann, Kareem Ismail, Robert A Kratzke

Abstract read
PubMed Publisher
In one paragraph

Article in Cancer gene therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
7.3field-weighted citation impact, top 3% 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

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

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  17. Navigating the Molecular Signaling: Deciphering Cancer Stem Cell Self-Renewal Pathways.International journal of molecular and cellular medicine · 2025
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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

7 authors at 3 institutions in 1 country.

Manish R PatelDepartment of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA. patel069@umn.edu.
Alexander DashDepartment of Biology, Macalester College, St. Paul, MN, USA.ORCID http://orcid.org/0000-0002-9337-3417
Blake A JacobsonDepartment of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
Yan JiHealth Partners, Regions Hospital, St. Paul, MN, USA.
Daniel BaumannDepartment of Biology, Macalester College, St. Paul, MN, USA.
Kareem IsmailDepartment of Biology, Macalester College, St. Paul, MN, USA.ORCID http://orcid.org/0000-0002-2597-1503
Robert A KratzkeDepartment of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
Macalester College · USUniversity of Minnesota Medical Center · USRegions Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The concept of using viruses to treat cancer has now shown proof of concept in several recent clinical trials, leading to the first FDA approval of virotherapy for melanoma last year. Vesicular stomatitis virus (VSV) is a promising oncolytic virus that has inhibitory effects on a number of cancer types including non-small cell lung cancer. One of the major mechanisms of resistance to VSV infection is the type I interferon (IFN) response, leading to the development of VSV expressing IFNβ which will lead to resistance of viral replication in normal cells which have intact IFN signaling but allow replication in cancer cells with defective IFNβ signaling. However, some cancer cells have intact or partially intact IFN signaling pathways leading to resistance to virotherapy. Here we utilized JAK/STAT inhibitor, ruxolitinib, in combination with VSV-IFNβ to see if inhibition of JAK/STAT signaling will enhance VSV-IFNβ therapy for lung cancer. We used five human and two murine NSCLC cell lines in vitro, and the combination treatment was assayed for cytotoxicity. We performed western blots on treated cells to see the effects of ruxolitinib on JAK/STAT signaling and PDL-1 expression in treated cells. Finally, the combination of VSV-IFNβ and ruxolitinib was tested in an immune competent murine model of NSCLC. Ruxolitinib enhanced virotherapy in resistant and sensitive NSCLC cells. The addition of ruxolitinib inhibited STAT1 phosphorylation and to a lesser extent STAT3 phosphorylation. Ruxolitinib treatment prevented NSCLC cells from enhancing PDL-1 expression in response to virotherapy. Combination ruxolitinib and VSV-IFNβ therapy resulted in a trend toward improved survival of mice without substantially effecting PDL-1 levels or levels of immune infiltration into the tumor. These results support further clinical evaluation of the combination of JAK/STAT inhibition with virotherapy.

Indexed as

Oncolytic VirotherapyAnimalsB7-H1 AntigenCarcinoma, Non-Small-Cell LungCell Line, TumorCombined Modality TherapyDisease Models, AnimalHumansInterferon-betaJanus Kinase InhibitorsLung NeoplasmsMiceNitrilesOncolytic VirusesPyrazolesPyrimidinesB7-H1 AntigenCD274 protein, humanInterferon-betaJanus Kinase InhibitorsNitrilesPyrazolesPyrimidinesruxolitinib

Identifiers

PMID30622322
OpenAlexW2908683838

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.