Glioblastoma multiforme (GBM) is the most common aggressive malignant primary brain tumor afflicting approximately 3.19 per 100,000 persons in the United States with an incidence 1.6 times higher in males compared to females. GBM usually arises from the glial cells known as astrocytes and it is commonly located in the supratentorial region (cortical lobes),usually affecting the frontal lobe. A unique feature of this tumor is its rapid local growth and spread making the prognosis very poor with a 5-year survival rate less than 5 %.Treatment of GBM remains challenging. Multiple therapeutic interventions are used for GBM including surgical resection of the tumor, radiotherapy and chemotherapy. Other experimental methods for the treatment of GBM include immune therapy, gene therapy, simulated microgravity therapy, and oncolytic viral therapy. We propose a combination therapy of simulated microgravity using a clinostat-based three-dimensional culture system with an oncolytic viral therapy using an autonomous rat parvovirus H-1 (H-1PV). Our hypothesis combines the beneficial effects of simulated microgravity and oncolytic viral therapy to lyse tumor cells through induction of apoptosis, decreased cell proliferation and or induction of an immune response. This proposal provides the foundations to construct novel breakthroughs in the treatment of GBM.