Pharmacologic and chemical adjuvants in tumor virotherapy

Oncolytic viruses (OVs) have been designed to replicate only in tumors that have either activation of specific ocogenes or inactivation of specific tumor suppressor pathways. There is a need to define a particular set of antiviral effectors responsible for limiting OV survival. These factors include cytokines, neutralizing antibodies, intracellular signaling cascades, cell-cycle checkpoints, and angiogenesis. As the important antiviral responses are defined, it is also critically important to understand the clinical implications that accompany the use of these drugs. A delicate balance must be achieved in identifying specifically targeted drugs that limit the essential antiviral pathways while also leaving the host uncompromised to defend against disseminated viral infection and replication. The challenge will be to determine which viruses work best for specific cancers while defining the proper dose, schedule route of administration, and appropriate treatment.