Improving the Efficiency of Alkylation Anticancer Chemotherapies
Alkylating agents are extensively used against a number of malignancies such as lymphoma, brain tumors, melanoma and Hodgkin’s disease. These agents kill tumor cells by damaging their DNA. However, repair of the DNA damage induced by these alkylating agents by human DNA repair proteins, especially the human AGT protein, significantly limits the efficacy of these treatments. Thus inhibiting these DNA repair activities in tumor cells is crucial for obtaining the maximum therapeutic effect for these treatments. By adopting a multidisciplinary approach that integrates chemistry, biology and structural study, Dr. Chuan He plans to fully elucidate the detailed interaction between the human AGT protein and its DNA substrates. With this knowledge more efficient inhibitors will be designed, prepared and tested to block the activity of this protein. Dr. He also plans to search for other DNA repair functions that could play major roles in tumor resistance towards DNA damaging chemotherapeutic agents. A proteomic technique that looks at proteins in the whole cell will be developed to achieve this goal.