Amelioration of Glioblastoma Multiforme via the Combination of Simulated Microgravity and Oncolytic Viral Therapy

Abstract

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. Arising from the glial cells known as astrocytes, GBM is commonly located in the supratentorial region (cortical lobes) affecting the frontal lobes. A unique feature of this tumor is its rapid local growth and spread making the prognosis very poor with a 5-year survival rate of 6.9%. The treatment of GBM remains challenging. Multiple therapeutic interventions are used for GBM, including the 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 oncolytic viral therapy using an autonomous rat parvovirus H1. Our hypothesis combines the beneficial effects of simulated microgravity and oncolytic viral therapy to lyse tumor cells through the induction of apoptosis, decreased cell proliferation and/or the induction of an immune response. This proposal provides the foundations to construct novel breakthroughs in the treatment of GBM.

Keywords

• brain tumor
• clinostat
• chromosomal loss
• epidermal growth factor receptor (EGFR)
• genetically modified viruses
• mutations