Virotherapy against malignant glioma stem cells

Abstract

Glioblastoma multiforme, the most common primary intracranial malignancy, is associated with very poor outcome despite advances in surgical techniques and chemo- and radiation therapy. Many novel treatment modalities are being investigated with varying amount of success. Evolution of cancer stem cell hypothesis provides a new venue for developmental therapeutics. In this review, we highlight the literature regarding the existence of glioma stem cells and their characteristics. We also discuss the potential for virotherapy, a novel therapeutic approach utilizing conditionally replicative viruses, to directly target this population of self-renewing cancer stem cells.

Figure 1. Cancer Stem Cell Hypothesis

According to cancer stem cell hypothesis, tumor burden in maintained by a small group of self renewing and differentiating cells, aka cancer stem cells (CSC). Conventional therapy targeting tumor bulk leads to tumor regression, however, presence of CSCs in the residual tumor leads to tumor recurrence. Goal of novel stem cell targeted therapy is to eradicate the population of CSC and absence of tumor sustaining CSCs will lead to tumor eradication overtime.

Figure 2. Stem cell targeted virotherapy

Viral vectors targeting cancer stem cells are genetically modified to recognize and multiply only in CSCs leading to destruction of CSCs and resulting in further infection of neighboring stem cells. Repetition of this cycle leads to eradication of the pool of multipotent CSCs which eventually leads to eradication of the tumor.