Related Experiment Video

Updated: Mar 8, 2026

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
08:51

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy

Published on: April 3, 2018

9.6K

Reovirus resistance in tumors mediated by elevated ISG expression: overcoming therapeutic resistance via JAK/STAT

Yuxin Yang1,2, Xiaojin Lin1,3, Liang Chen4

  • 1Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, Guiyang, Guizhou, China.

Virology Journal
|March 6, 2026
PubMed
Abstract

Insights

Tumor cells resistant to reovirus therapy show higher interferon-stimulated gene (ISG) expression. Inhibiting the JAK-STAT pathway can overcome this resistance, improving oncolytic virus efficacy.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Reovirus shows promise for cancer therapy, but efficacy is limited by tumor cell resistance.
  • Understanding molecular mechanisms of reovirus resistance is crucial for improving cancer treatment outcomes.

Purpose of the Study:

  • To investigate the molecular basis of tumor cell resistance to reovirus.
  • To identify therapeutic strategies to overcome reovirus resistance.

Main Methods:

  • Assessed reovirus sensitivity in 12 tumor cell lines.
  • Performed transcriptomic analysis on ovarian cancer cells with differing reovirus responses.
  • Modulated the JAK-STAT pathway using RO8191 and ruxolitinib.
  • Tested patient-derived breast cancer cells for cross-resistance.

Main Results:

  • Tumor cells stratified into sensitive, moderate, and resistant groups based on viability.
  • Reovirus-resistant cells exhibited higher baseline interferon-stimulated gene (ISG) expression, including interferon-related DNA damage resistance signature (IRDS) genes.
  • JAK-STAT pathway inhibition reduced ISGs and enhanced reovirus oncolysis.
  • Upregulated ISGs and IRDS may contribute to cross-resistance with chemotherapy.

Conclusions:

  • Elevated baseline ISG expression is linked to reovirus resistance.
  • The JAK-STAT pathway and U-ISGF3 may mediate IRDS upregulation, contributing to resistance.
  • These findings offer a basis for enhancing reovirus therapy in resistant cancers.
Keywords:
IRDSISGJAK-STATOncolytic virusReovirusResistanceU-ISGF3

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