Cancer is the second leading cause of death worldwide. There are many anti-cancer treatments, however, such treatments are very harsh for the patients, have significant toxicity and are inefficient. The low efficacy attributed to anti-cancer treatment creates an urgent need for innovative therapeutic strategies. One such strategy utilizes live viruses that have selective cancer-killing properties (oncolytic viruses), such as Vesicular Stomatitis Virus (VSV). This virus is relatively non-pathogenic to humans, and preferentially infects cancer cells, which lack specific antiviral pathways. However, oncolytic virotherapy is in its infancy and must overcome several obstacles, as for example the spread of uncontrollable replication on normal cells. We have previously shown that VSV replication can be modulated with a class of drugs (statins) normally used to treat hypercholesterolimea. That work resulted in a patent for controlled viral oncolysis and has the potential to become a novel anti-cancer treatment. We have shown that statins modulate viral replication, and antiviral cellular gene expression in infected cells pretreated with statins. However, the extent of our gene expression investigation was preliminary. Here we propose an extensive investigation of cancer cell gene expression upon statin treatment and viral infection. In order to accomplish this, we will (Specific Aim I) measure expression of all cellular transcripts using the latest state-of-the-art technology RNAseq, which is an unbiased discovery tool. Furthermore, we will (Specific Aim II) use bioinformatics tools to correlate gene expression obtained in Specific Aim I for identification of specific pathways that can be further targeted for controlled oncolytic virotherapy. Our systematic approach using RNAseq and bioinformatics will most likely reveal previously unknown transcripts that are important for cellular antiviral defense. Results of this study will be auxiliary to the development of viral anti-cancer treatment, which can be more effective than current available treatments and less harsh on patients.