Oncolytic Viral Therapy with Gravity Approaching Zero to Ameliorate Glioblastoma Multiforme ^†

Abstract: 

Glioblastoma multiforme (GBM) is the most common aggressive malignant primary brain tumor, afflicting approximately 3 in every 100,000 persons in the United States, with an incidence rate that is 1.6 times higher in males compared to females. Arising from the neural and/or glial progenitor/stem cells, GBM is commonly located in the supratentorial cortical region affecting the frontal lobes. The rapid local growth and spread of GBM leads to a dismal prognosis with a 5-year survival rate of 6.9%, despite multiple therapeutic interventions, including surgery, radiotherapy, and chemotherapy. To overcome the challenge to develop curative treatments of GBM, several promising experimental methods (gene therapy, immune therapy, oncolytic viral therapy, and simulated microgravity therapy) are under investigation. Potentially beneficial effects of microgravity on GBM include (A) the repression of survival signaling pathways, (B) the induction of the apoptosis of cancerous cells, and (C) the blocking of spherical colony formation and cellular proliferation via the downregulation of ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related (ATM/ATR) and cyclin-dependent kinase 1/2 (CDK1/2) proteins to block cellular phase 2 to progress to G2. Our hypothesized combination of oncolytic viral therapy using an autonomous rat parvovirus H1 with simulated microgravity utilizing the potentially beneficial effects of microgravity on tumor cells (decreased cell proliferation, disrupted mitochondrial functions, and the induction of apoptosis) [1] was limited using simulated microgravity on earth. We now propose to conduct similar investigations on space stations where gravity approaches zero. We hypothesize that oncolytic viral therapy in space without gravity will (A) lyse tumor cells through the induction of apoptosis, decreased cell proliferation, and the induction of an immune response, and (B) constitute the foundation of potentially curative treatments of GBM.