Oncolytic viruses for the therapy of brain tumors and other solid malignancies: a review.
In spite of significant advances in the understanding of molecular processes in tumor biology that have led to the development of oncologic therapeutic strategies, the prognosis for several types of tumors (such as brain, pancreas, or hepatic malignancies) remains dismal. Without question, a strong need exists for continued investigations in new agents and new therapeutic regimens. The realization that several genes used by viruses in their lytic life cycle interact and/or complement the function of genes employed by cells in cellular events linked to cell cycle progression, apoptosis, and/or metabolism immediately suggests the development of treatment strategies wherein viral mutants could be employed as selective anticancer agents. Such viruses (designated as oncolytic viruses) can selectively grow in tumor cells, produce viral progeny in those cells, lyse them and release this progeny that can then infect additional cells in the tumor mass. A theoretical advantage of oncolytic viruses (OV) is that their numbers should augment within the tumor mass, a property that is lacking with drugs or radiation treatments. Additionally, Ovs' mode of tumor killing differs from standard anticancer agents, providing the possibility for synergistic interactions in multimodal tumor therapies. In this review, we will describe the development of OVs and briefly review the life cycle of their wild-type (wt) counterparts. We will also summarize published results from OV clinical trials and attempt to provide a perspective on research in this area.
Fulci
Giulia
G
Molecular Neuro-Oncology Laboratories, Massachusetts General Hospital-East Building, CNY6, 13th Street, Charlestown, MA 02129, USA. gfulci@partners.org
Chiocca
Ennio Antonio
EA
D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy* / Q000821:virology*; D002986:Clinical Trials as Topic; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000628:therapy* / Q000821:virology*; D014780:Viruses / Q000235:genetics*