National Cancer Institute 1R15CA290568-01

Harnessing the potential of pharmacological small molecules to amplify VSV-based oncolytic viral therapy

This award funds research to enhance VSV-based oncolytic viral therapy for melanoma by inhibiting the PI3K/AKT/mTOR pathway and engineering a hybrid virus, aiming to improve cancer treatment efficacy and support biomedical education and infrastructure.

Description

The project hypothesizes that local inhibition of the PI3K/AKT/mTOR signaling pathway in tumors will facilitate the intratumoral spread of oncolytic viruses, specifically VSV, leading to cancer cell death and tumor growth delay. The research involves engineering a hybrid VSV virus (VSV-MORV-G [VMG]) to improve safety and potency, and using natural compounds like fisetin to inhibit mTOR and S6K1 kinases, thereby enhancing the oncolytic effect. The study aims to test these strategies in cell lines and preclinical animal models of melanoma, with the goal of developing novel pharmacovirotherapy approaches for melanoma and other cancers. Funding will support biomedical research, student training, education, and infrastructure development at the SUBR College of Sciences and Engineering and College of Nursing and Allied Health.

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