Development of armed oncolytic agents based on the herpes simplex virus type 1 for the treatment of glioblastoma

Glioblastoma (GBM) is one of the most common and aggressive malignant brain tumors in adults. Patients affected by glioblastoma show poor prognosis and low survival rate after the diagnosis. Indeed, nowadays, glioblastoma is mostly untreatable and intervention procedures rely on classic, no-specific treatments, such as surgical resection followed by radiotherapy and chemotherapy. Part of the difficulties in the treatment of glioblastoma arises from the complex molecular background of the cancerous cells and from the high heterogeneity in the genetic processes that lead to the development of the tumor. New approaches are under evaluation, including new prediction techniques and innovative therapies, like immunotherapy. Among the novel therapeutic strategies, oncolytic viruses that specifically replicate in and kill tumor cells are emerging as interesting alternatives. Furthermore, oncolytic viruses can be engineered for targeting particular signal pathways. Herpes simplex virus type I (HSV-1) is the focus of the present study, in which the virus, used in its oncolytic form, was armed with different therapeutic genes or modified in order to improve its delivery and killing activity toward the tumor cells.