Glioma-Parvovirus Interactions: Molecular Insights and Therapeutic Potential

Abstract

Brain tumours remain one of the most devastating diseases of modern medicine. Although they only represent approximately 1.9% of primary tumours in Europe, their mortality is around 70% and they are within the group of the 10 cancer types causing the highest yearly mortality rate. Gliomas are malignancies of neuroepithelial origin and represent 40-60% of brain tumours. In particular, glioblastoma multiforme (GBM, astrocytic tumours of type IV) is the most aggressive and frequent of primary brain tumours, representing 60% of gliomas. Despite clinical practice advances, the mean survival time of GBM patients has not improved significantly within the last few decades, and it remains around 12-15 months. Current standard of care includes maximal safe surgical resection, and a combination of radio- and chemotherapy with concomitant and adjuvant temozolomide or carmustine wafers (Wen and Kesari 2008). At the moment, the clinical improvement reached is modest, with a 5-year survival rate of less than 5% (Mangiola et al. 2010). The poor results obtained with conventional therapies may be explained by their relatively unspecific nature (Newton 2010), the inefficient delivery of many drugs to the tumoral tissue due to the blood-brain and blood-tumour barriers, as well as by the intrinsic radio- and chemo-resistance of GBM (Newton 2010). In light of the limitations of conventional treatment strategies, the necessity of new approaches that would be more effective against GBM became evident. The current understanding of the molecular biology of GBM has set researchers on the path of more targeted and specific therapies exploiting the molecular properties of the tumour. Most targeted agents are tyrosine kinase inhibitors, or monoclonal antibodies directed against either cell surface growth factor receptors or intercellular signaling molecules (angiogenesis) (Van Meir et al. 2010). The overall experience of the monotherapy with targeted agents has shown limited efficacy, with response rates of less than 10-15% and no prolongation of survival (Clarke et al. 2010; Van Meir et al. 2010). Other promising therapies for GBM are also currently being investigated, including combined therapy with targeted agents, immunotherapy, gene therapy, or oncolytic virotherapy (Clarke et al. 2010; Van Meir et al. 2010).