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Updated: Jul 20, 2025
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Looking for biomarkers in interferon response pathway to predict response to oncolytic HSV-1 in breast cancer: An ex
Zahra Nejatipour1, Ladan Teimoori-Toolabi2, Ramin Sarrami Forooshani3
1Genetics and Molecular Medicine Department, Zanjan University of Medical Science, Zanjan, Iran.
Abstract:
Breast cancer is the most common malignancy in women worldwide. Administration of oncolytic viruses is one of the novel promising cancer therapy approaches. Replication of these viruses is usually limited to cancer cells that have interferon (IFN) signaling defects. However, Interferon signaling is not completely impaired in all cancer cells which may limit the benefits of virotherapy. Identification of realistic IFN-mediated biomarkers to identify patients who most likely respond to virotherapy would be helpful. In this study, eight patients-derived primary tumor cultures were infected with an ICP34.5 deleted oHSV, then the rate of infectivity, cell survival, and expression of the gene involved in IFN pathway were analyzed.Data showed that mRNA expressions of Myeloid differentiation primary response protein (Myd88) is significantly higher in tumors whose primary cultures showed less cell death and resistance to oHSV infectivity (P-value < 0.05). The differentiating cut off of Myd88 expression, inferred from the receiver operating characteristic (ROC) curve, predicted that only 13 out of 16 other patients could be sensitive to this oHSV. Identifying such biomarker improves our ability to select the patients who do not exhibit resistance to virotherapy.
Insights
Myeloid differentiation primary response protein (Myd88) is a potential biomarker for breast cancer virotherapy. Higher Myd88 expression indicates resistance to oncolytic virus treatment, aiding patient selection.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Breast cancer is a leading global malignancy in women.
- Oncolytic viruses offer a promising cancer therapy, but their efficacy can be limited by intact interferon (IFN) signaling in cancer cells.
- Identifying biomarkers for IFN-mediated responses is crucial for predicting virotherapy success.
Purpose of the Study:
- To identify interferon (IFN)-mediated biomarkers that predict patient response to oncolytic virus therapy in breast cancer.
- To evaluate the correlation between Myd88 gene expression and sensitivity to oncolytic herpes simplex virus (oHSV) in patient-derived tumor cultures.
Main Methods:
- Eight patient-derived primary breast tumor cultures were infected with an ICP34.5 deleted oncolytic herpes simplex virus (oHSV).
- Infectivity rates, cell survival, and gene expression within the IFN pathway were analyzed.
- Receiver operating characteristic (ROC) curve analysis was used to determine a differentiating cutoff for Myd88 expression.
Main Results:
- Tumor cultures with higher Myeloid differentiation primary response protein (Myd88) mRNA expression exhibited reduced cell death and resistance to oHSV infectivity (P < 0.05).
- The identified Myd88 expression cutoff predicted sensitivity to oHSV in only 13 out of 16 additional patients.
- Myd88 emerged as a significant biomarker for predicting resistance to oHSV virotherapy.
Conclusions:
- Myeloid differentiation primary response protein (Myd88) mRNA expression is a potential predictive biomarker for breast cancer response to oncolytic virus therapy.
- Elevated Myd88 levels indicate resistance to oHSV, enabling better patient selection for virotherapy.
- This biomarker can improve the efficacy of virotherapy by identifying patients most likely to benefit from treatment.
