ASO Author Reflections: The Role of Oncolytic Virotherapy in Advanced Gastrointestinal Cancers

Abstract

The origins of oncolytic virotherapy are rooted in the astute observations of clinicians who documented regression of certain malignancies following infections with naturally occurring viruses. By the mid-1900s, many clinical trials employed naturally occurring viruses (e.g. hepatitis, West Nile) for the treatment of cancer, but efficacy was limited and toxicities were common secondary to the off-target effects of viral inoculation. As genetic engineering further developed and recombinant DNA technology became more widespread in the 1990s, there was great interest in modifying viral genomes to improve cancer selective replication. One prime example of this was reported by Martuza et al., who described a mutant herpes simplex virus (deficient in the thymidine kinase gene) that was effective at treating gliomas while minimizing effects on surrounding normal brain tissue. In the years that followed, there was ever-increasing interest in modifying viral genomes (including those of adenoviruses, herpes viruses, vaccina viruses, etc.) to increase the potential for cancer treatment.