In a recent clinical trial, combining the rarely used cancer drug cediranib with the more mainstream drug olapraib treated recurrent ovarian cancer better than olaparib alone—a surprising finding. Now, Yale researchers have discovered exactly how cediranib works and why it might be useful in combination with other treatments.
The team, led by Peter M. Glazer, MD, PhD, chair and Robert E. Hunter Professor of Therapeutic Radiology, and professor of genetics, studied the drug using isolated human cancer cells as well as human tumors in mice. They found that cediranib, in addition to its known role in blocking blood vessel formation, also stops a cellular program called homology-directed DNA repair. Tumor cells rely on this program to repair their DNA when it is damaged by such treatments as radiation or chemotherapy.
While other drugs block molecules involved in homology-directed DNA repair, cediranib works at an earlier stage, affecting the expression of genes involved in the process, the researchers reported May 15 in Science Translational Medicine.
Combining cediranib with DNA-damaging agents could deliver a double blow to cancer cells, the new results suggest.