Elucidating the Sensitizing Mechanism of Cancer Radiosensitizers at the Molecular Level

Radiation therapy for cancer treatment is based on the use of ionizing radiation to break chemical bonds in malignant cells, thereby causing DNA damage and leading to cell death. Radiosensitizers are compounds that are used to make tumor cells more sensitive to radiation therapy. In this project, we will use a combination of state-of-the-art experimental and simulation techniques from molecular physics, to investigate the fundamental mechanism of X-ray-induced photofragmentation (bond breaking) in radiosensitizers and sensitized DNA oligomers. The planned work goes beyond previous similar studies by carefully considering the effect of the aqueous environment of the sensitizer or the DNA oligomer on its fragmentation behavior. We will compare the identified fragmentation pathways with the results of clinical trials of radiosensitizers, to determine structure-property relationships that can guide the development of new and more effective sensitizers in the future.