Chemotherapy and Oncolytic Virotherapy: Advanced Tactics in the War against Cancer

Abstract

Cancer is a traitorous archenemy that threatens our survival. Its ability to evade detection and adapt to various cancer therapies means that it is a moving target that becomes increasingly difficult to attack. Through technological advancements, we have developed sophisticated weapons to fight off tumor growth and invasion. However, if we are to stand a chance in this war against cancer, advanced tactics will be required to maximize the use of our available resources. Oncolytic viruses (OVs) are multi-functional cancer-fighters that can be engineered to suit many different strategies; in particular, their retooling can facilitate increased capacity for direct tumor killing (oncolytic virotherapy) and elicit adaptive antitumor immune responses (oncolytic immunotherapy). However, administration of these modified OVs alone, rarely induces successful regression of established tumors. This may be attributed to host antiviral immunity that acts to eliminate viral particles, as well as the capacity for tumors to adapt to therapeutic selective pressure. It has been shown that various chemotherapeutic drugs with distinct functional properties can potentiate the antitumor efficacy of OVs. In this review, we summarize the chemotherapeutic combinatorial strategies used to optimize virally induced destruction of tumors. With a particular focus on pharmaceutical immunomodulators, we discuss how specific therapeutic contexts may alter the effects of these synergistic combinations and their implications for future clinical use.

Modelling the spatiotemporal dynamics of chemovirotherapy cancer treatment

“…These simulation results assert that combining chemotherapy and virotherapy to treat cancer is more effective and a good alternative to either chemotherapy or virotherapy alone, which is in agreement with the latest experimental studies [3,6,8,12,23,24,43,45,49,61,62]. These studies have shown that the right combination of oncolytic viruses and chemotherapy agents resulted in enhanced therapeutic effects not attainable by either therapy alone.…”

“…Numerous experimental studies have shown that, with the right combination of oncolytic viruses and standard cytotoxic chemotherapy agents, synergistic interactions occur resulting in enhanced therapeutic effects not attainable by either therapy alone [6,43,45,49]. Chemovirotherapy has been experimentally and clinically tested for the treatment of some cancers such as malignant gliomas [3,61], lymphoma [62], lung cancers [23], and metastatic breast cancer [12].…”

“…Primarily, this is due to the complexity and the high non-linearity of the dynamics between tumour cells, oncolytic viruses, and their microenvironment [43,45]. There is increasing evidence that mathematical models can be helpful in investigating the interactions between tumour cells and viruses.…”

Unlocking the Promise of Oncolytic Virotherapy in Glioma: Combination With Chemotherapy to Enhance Efficacy

“…OVs expressing enzymes, antigens and/or cytokines may have particular utility in combination with chemotherapy. Genes previously studied with OV and found to increase their efficacy via induction of cell death include TRAIL, FasL, Ki-67 and others [119,120]. Expressible cytokines under investigation include IL-2, I IL-4, IL-18, IL-24, TNF-α and GM-CSF [119].…”

“…Genes previously studied with OV and found to increase their efficacy via induction of cell death include TRAIL, FasL, Ki-67 and others [119,120]. Expressible cytokines under investigation include IL-2, I IL-4, IL-18, IL-24, TNF-α and GM-CSF [119]. IL-12 is of particular interest because it promotes the cytotoxic activity of NK cells and CD8+ T lymphocytes [121].…”