Recent advances in virology and cell biology have established the concept of “oncolytic viruses”, which preferentially replicate in and destroy cancer cells with minimal destruction of normal cells. Their ability to selectively kill cancer cells was demonstrated in basic research and preclinical animal studies, leading to a number of clinical trials evaluating the efficacy of oncolytic viruses. Oncolytic herpes virus was approved by the FDA for the treatment of melanoma in 2015. This well-established pipeline between basic and clinical research has created an exciting and promising area of virology where basic research can be directly applied to impact the health of Canadians in the important area of cancer therapy.

　Oncolytic viruses exploit tumor-specific cellular changes for their selective replication, including p53 deficiency, oncogenic Ras activation, insensitivity to type I interferon (IFN) and viral receptors uniquely expressed on cancer cells. Our previous research showed that activation of the Ras/MEK pathway suppresses the host antiviral response induced by IFN (J. Virol., 2006). This is caused by suppression of the transcription of a group of IFN-inducible genes including STAT2, RIG-I, GBP2 and IL15 (J. Virol., 2009, PLoS ONE 2012). Our research further showed that this suppression is brought about by downregulation of interferon regulatory factor 1 (IRF1), the transcriptional regulator of the IFN-inducible genes (Oncogene, 2015, Cancer Letters 2015, PLoS ONE 2016). Together, these studies demonstrated that the Ras/MEK downregulation of IRF1 is one of the major mechanisms underlying viral oncolysis. Our current research demonstrates that Ras/MEK promotes one of IRF1 posttranslational modifications, SUMOylation, which regulates IRF1’s transcriptional activity.

　Our identification of IRF1 as core target of the Ras/MEK pathway underlying viral provides a landmark around which new detail uncovered will deliver a new array of therapeutic targets.

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