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. Furthermore, we will test DC10 in combination with radiotherapy in mice with tumors that has spread to other organs, and we will investigate how DC10 is absorbed, distributed metabolised in the body. Side effects of long-term treatment with DC10 will be investigated. Data generated through these experiments will provide a foundation for further work aiming to bring DC10 into clinical use as a radiosensitiser.