A METHOD FOR INCREASING THE REPLICATION OF ONCOLYTIC HSVS IN HIGHLY RESISTANT TUMOR CELLS USING MTOR PATHWAY AND PI3K INHIBITORS

摘要

The present invention is directed to the administration of an HSV derived oncolytic virus and a PBK/AKT/mTOR pathway inhibitor to treat various types of resistant tumors. Therapy-resistant tumor formation is one of the main causes for treatment failure in the clinic. The treatment methods and compositions disclosed herein sensitize resistant tumors to the treatment of herpes simplex virus (HSV)-based oncolytic virotherapy. Pre or co-treatment of resistant tumor cells with the mTOR inhibitor, rapamycin, or certain PI3K inhibitors, such as LY294002, can efficiently sensitize the tumors to HSV derived oncolytic viruses, whereby the replication and spread of the viruses are dramatically enhanced.