The Effects of Selinexor Concentration and Time on the Myxoma Virus

Cancer is one of the leading causes of death, globally, with an estimated 9.6 million deaths in 2018, according to the World Health Organization. However, this is not the only impact cancer has on affected individuals, as death rates only capture the mortality of cancer, there are still detrimental effects cancer has on quality of life. Newer therapies for cancer attempt to circumvent these unwanted detriments, such as hormone therapy, stem cell transplants, targeted therapy, etc.3. One such novel therapy being virotherapy, which is the subject of this study. This study follows the observations of the myxoma virus (MYXV), a prototypic poxvirus which belongs to the Leporipoxvirus genus of the Poxviridae family. This method allows larger particles to enter host cells through the process of overriding host cell endocytosis pathways, with a few exceptions. Interestingly, research has shown that MYXV has been able to infect multiple types of tumor cells of non-rabbit species both in vitro and in vivo, in not only humans but murine, rodent, species as well. This allows MYXV to pose as a potential virotherapy for human cancer cells. McFadden research lab has been researching the role of the exportin 1 protein (XPO1), also known as the chromosome maintenance region-1 (CRM-1). It is suspected that the XPO1 pathway may be one of the evasion mechanisms that MYXV utilizes as an antiviral response. KPT-330 (Selinexor) is a selective inhibitor of nuclear transport (SINE) drug that was designed as the first-in-human oral FDA approved cancer treatment. It has been shown effectiveness in inhibiting XPO1 in multiple lines of cancer cells, such as the Lewis Lung Carcinoma (LLC1) cells researched in this study. McFadden research lab has been examining the effects of various Selinexor concentrations along with different multiplicities of infection (MOIs) of MYXV to determine the best combination that can be used to reduce tumor size at the highest effectiveness. Overall, Selinexor is not increasing cell killing through a synergistic means, but rather simply by increasing the ability of MYXV to infect and spread in LLC1 cells. This then causes increased cell killing given that more LLC1 cells are penetrated by the OV and “suffocated” by the prevention of exporting essential proteins from the nucleus to their respectively critical final destinations in the cancer cells.