Study Highlights Cancer Metabolism and Virus-Driven Therapy
The Warburg Effect and Nutrient Dependence
Recent research has revealed mechanisms that influence the relationship between cancer metabolism and the efficacy of virus-driven targeted therapies. For many years, it has been established that cancer cells significantly increase their glucose consumption to support rapid growth, a phenomenon known as the Warburg effect. This enhanced glucose utilization in cancer cells stands in stark contrast to normal cells. Consequently, extensive research has aimed to leverage this aspect of cancer metabolism for therapeutic purposes.
In addition to glucose, cancer cells also rely heavily on glutamine to synthesize essential macromolecules necessary for cellular growth. A recent study led by Dr. Leonard Seymour’s group at the University of Oxford has explored how to manipulate cancer cells’ dependence on these nutrients to improve the effectiveness of virus-powered targeted therapies.
Oncolytic Viruses in Cancer Treatment
Oncolytic viruses are gaining traction as a targeted cancer treatment option. This class of therapy includes viruses engineered to identify and infect cancer cells specifically, leaving healthy cells unharmed. Once inside the cancer cells, these viruses replicate rapidly, leading to the destruction of the cancer cells and the subsequent release of additional viral particles.
Enhancing Virus-Directed Therapy Effectiveness
The Oxford University research team demonstrated that pharmacologically blocking certain metabolic pathways and reducing the availability of key nutrients in lung and ovarian cancer cells significantly improved the effectiveness of therapeutic oncolytic viruses. Their findings were published in *Cancer Research*.
These strategies not only facilitated faster replication of viral particles within cancer cells but also increased the expression of critical targeting antigens unique to cancer cells. Interestingly, the study found that cancer cells treated initially with oncolytic viruses adapted by increasing their glucose and glutamine uptake.
The Need for Clinical Trials
Encouragingly, similar results were observed in mouse models, where alterations in cancer metabolism enhanced the efficacy of viral therapy and led to considerable reductions in tumor growth. While these findings are promising, researchers emphasize the necessity of validating these results in clinical trials to assess the relative effectiveness of this approach across various types of cancer cells.
Written by Vinayak Khattar, Ph.D., M.B.A.
Reference: Dyer, A., Schoeps, B., Frost, S., Jakeman, P. G., Scott, E. M., Freedman, J., & Seymour, L. W. (2018). Antagonism of glycolysis and reductive carboxylation of glutamine potentiates activity of oncolytic adenoviruses in cancer cells. *Cancer Res*. doi:10.1158/0008-5472.CAN-18-1326