Because cancer cells can acquire resistance to radiation, Sekhar Konjeti, Ph.D., Michael Freeman, Ph.D., and colleagues are searching for ways to enhance the DNA damage produced by ionizing radiation in order to overcome cancer cell resistance.
The investigators have now identified a novel chemical entity (YTR107) that enhances the sensitivity of several different cancer cell lines to radiation. They report Aug. 30 in Clinical Cancer Research that YTR107, which has been patented by Vanderbilt, targets a protein called nucleophosmin that has a role in DNA repair. They demonstrated that YTR107 blocks phospho-nucleophosmin shuttling to the sites of radiation-induced DNA damage.
These findings support the idea that blocking DNA damage repair – through a novel pathway (nucleophosmin shuttling) – is an effective strategy for sensitizing cancer cells to the killing effects of ionizing radiation and increasing the efficacy of radiation therapy.