DC10 - a novel drug against cancer radioresistance

50% of cancer patients receive radiotherapy, but it has limited effect when the tumor has spread from its primary site to other regions. These cases account for 2/3 of cancer-related deaths, i.e. more than 12 million fatalities each year. Thus, radioresistance is a major cause of human suffering and lost years globally. However, radiation therapy has become more accessible due to a 5-fold increase in the number of radiotherapy machines in the world since 1980. A radiosensitiser that potentiates the efficacy of radiotherapy could therefore improve the prognostic outlook for many patients. Sulfasalazine, which is used against inflammatory bowel disease and arthritis, also blocks cancer cells' production of anti-oxidants that protect against radiation. It amplifies the effect of a single radiation dose to cancer cells, but is unsuitable for use in cancer patients since radiation treatment is delivered over several weeks. Administering sulfasalazine over this time period previously caused severe side effects in cancer patients, probably due to the fact that they are weakened by their disease, as well as by side effects from chemotherapy. Using sulfasalazine as a starting point, we conducted molecular structure-optimisation resulting in derivatives of sulfasalazine which also block the production of anti-oxidants. Amongst them, the drug candidate DC10 was tested on several cancer cells type in the laboratory and on melanoma in mice, and exhibited efficacy similar to sulfasalazine. Initial studies suggest that DC10 is well tolerated with few side effects. With funds from the NFR, we have carried out pharmacological mapping which indicates that DC10 is absorbed across the intestinal wall and is relatively stable in terms of breakdown in the liver and with a long half-life in the bloodstream. We therefore want to test DC10 in combination with radiotherapy on mice with more advanced stages of cancer where there is spread, and we want to map how the drug is taken up, distributed and converted. In addition, acute and chronic side effects of long-term treatment with DC10 will be investigated. The knowledge this provides will form the basis for further work on taking DC10 into clinical use to enhance the effect of radiotherapy for cancer patients.