Taken together, these data show (i) that CSDE1 is a major positive regulator of VSV replication; (ii) that CSDE1P5S acts as an inhibitor of VSV replication facilitating escape from viral oncolysis; (iii) and that, although tumor cells readily evolve to escape viral therapy (CSDE1WT to CSDE1P5S), the oncolytic virus can, if given sufficient time, also itself evolve to complement those mutations that occur in its replication substrate. The gene discussed is CSDE1; the disease is neoplasm.