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Updated: May 28, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Molecular network pathways and functional analysis of tumor signatures associated with development of resistance to

T-J Song1, D Haddad, P Adusumilli

  • 1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Cancer Gene Therapy
|October 22, 2011
PubMed

Insights

Researchers identified gene expression changes in cancer cells resistant to oncolytic virus therapy. These findings reveal mechanisms of resistance and potential targets to improve viral cancer treatments.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Replication-competent attenuated herpes simplex viruses show promise in cancer therapy.
  • Mechanisms of resistance to oncolytic viral therapy are largely unknown.

Purpose of the Study:

  • To investigate gene expression changes in cancer cells that confer resistance to oncolytic viral therapy.
  • To identify molecular targets for overcoming resistance to oncolytic viruses.

Main Methods:

  • Developed therapy-resistant colon (HT29) and hepatoma (PLC5) cancer cell lines using oncolytic virus G207.
  • Analyzed gene expression patterns using complementary DNA microarray chips.
  • Examined gene expression in the context of molecular networks, pathways, and gene ontology.

Main Results:

  • Resistant cell lines exhibited 200- to 400-fold resistance to viral cytotoxicity compared to parental lines.
  • Microarray analysis revealed significant alterations in gene expression related to viral attachment, entry, nucleotide pools, and apoptotic pathways.
  • Identified specific gene expression signatures associated with resistance to oncolytic viral therapy.

Conclusions:

  • Gene expression changes in cell surface proteins, nucleotide metabolism, and apoptosis pathways contribute to resistance against oncolytic viruses.
  • The identified gene expression signatures offer potential targets to enhance the efficacy of oncolytic viral therapy.
  • Molecular assays may aid in patient selection for oncolytic virus treatment trials.

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