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Feasibility study for a First in Class radiosensitizer in models of cancer treatment.

Alternative title: Utvikling og testing av medikament for å potensiere effekten av strålebehandling for kreft.

Awarded: NOK 0.50 mill.

Development and validation of a radiosensitiser for cancer treatment. Many cancer types exhibit limited sensitivity towards radiotherapy. Accordingly, a definite cure can often not be achieved in the advanced stage. In some malignancies, this is mediated by increased synthesis of anti-oxidants that protect against harmful radiation effects. Notably, the drug Sulfasalazine which has been used to treat inflammatory bowel disease has also been shown to block synthesis of the anti-oxidant Glutathione. Previously, we reported that Sulfasalazine sensitized cancer cells towards radiotherapy by inhibiting Glutathione synthesis. However, its uptake is limited since most of the drug is degraded in the intestines, and administering the substance to heavily pre-treated cancer patients often trigger significant side effects. Therefore, we have tried to develop a radiosensitiser for cancer treatment through modifying the molecular structure of Sulfasalazine in order to increase stability and reduce side effects. Recently, we have developed a substance that inhibits Glutathione synthesis more effectively than Sulfasalazine. In this project, we plan to test this synthetic compound in melanoma, breast and brain cancer as these cancer types also display limited radiosensitivity. This will involve laboratory as well as animal experiments to determine therapeutic dose and the effect on the tumors when administering the test drug in combination with radiotherapy compared to radiotherapy alone. Blood samples, organs and tumor tissue from the animals will be examined and analysed to assess drug absorption from the intestines to the blood, tumor uptake, metabolism and excretion from the organism. Finally, then animals will be clinically examined and closely monitored for side effects. If results are encouraging, more extended pre-clinical testing will be conducted and a protocol will be established to scale up production of the compound for a clinical trial.

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