Terapia virale oncolitica: angoli di attacco

Oncolytic virus therapy is a rapidly developing way of treating cancer – the leading cause of death all around the world. Through direct interaction with tumor cells, or through inducing the immune system to fight against the disease, these virus-based anti-cancer agents are at the forefront of cancer therapy research. Throughout the last 25 years, it has become clear that oncolytic virus therapeutics are not likely to be effective on their own in most cases, but have to be used in combination strategies, with a clearer understanding of cancer biology. The interactions with host cancer cells, with the tumor microenvironment, and with the cells of the human immune system are some of the ways that oncolytic viruses exude their therapeutic effect. In this work, each of these aspects is examined, with research papers and review papers alike. First, the immunomodulatory activity of regular viruses, allowing them to infect and affect the healthy human biology, can be deactivated, to engineer viruses that mediate tumor-specific killing with little to no off-target damage. In its place, there is another way to affect the potential of oncolytic viruses – sensitizing tumors to immunotherapies. To that end, the viruses can be armed to target specific proteins, and inflame the tumor microenvironment. Next, the effects of changes in the host cells may be beneficial to replication and oncolytic activity of viruses. As an example, the effect of chemically induced ER stress, and subsequent Ca2+ influx, lead to increase in viral protein levels, increase in expression of viral DNA polymerase, genome replication, late viral protein expression and cell killing. This effect was found to be due to a signaling pathway between protein kinase C and E1A. This particular finding raised the possibility of using Ca2+ flux-modulating agents as a supplement to oncolytic virotherapies. Among the many ways to potentiate the oncolytic virotherapy, it is important to recognize the most effective and acknowledge the limitations and challenges associated with each of them. The search for the new ways to combat cancer is never-ending, but oncolytic viruses provide an elegant and biology-based agents that are customizable and potentially less toxic and dangerous than many therapeutics widely used today.