RATIONAL COMBINATION OF ONCOLYTIC VIRUSES AND RAPAMYCIN ANALOGUES IN CANCER THERAPY (LITERATURE REVIEW)
Abstract
Malignant neoplasms are currently one of the main causes of death in most countries of the world, and therefore the issue of developing new drugs for the treatment of cancer is extremely acute. Among the possible promising ways to combat it, the use of drugs containing oncolytic viruses and drugs based on rapamycin attracts attention. Oncolytic viruses (viruses that mainly affect cancer cells) have a direct cytolytic effect, destroying a malignant tumor, and also stimulate the antitumor immunity of the body. Rapamycin is a potent inhibitor of the mTOR -mechanical (formerly mammalian) target of rapamycin signaling pathway. It has been proven that rapamycin and its analogues can be effectively used for the treatment and prevention of cancer, as well as affect the aging process. While each group of drugs individually has certain disadvantages, there is a possibility of leveling them when used together, which in a number of studies has shown a good therapeutic result. The synergistic effect of oncolytic viruses and rapamycin is primarily due to the ability of the latter to stimulate the replication of the virus in the affected cells, showing its own cytostatic effect in the unaffected ones. Replication stimulation can occur through Akt activation or through suppression of mTORC1-dependent interferon type I production. Also, the catalytic inhibitors mTORC1 and mTORC2 enhance the replication of the herpes simplex virus in cancer cells along the eIF4E/4EBP axis. The mechanisms of action of oncolytic viruses, rapamycin and their combinations on malignant cells are considered in this literature review.
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