Grant: Proof of Principle Program - Phase I

Radiotherapy and many chemotherapeutic agents used in the treatment of cancer kill the cancer cells by damaging the DNA within the cells. Resistance to the treatment can arise because cells possess enzymes that can repair DNA damage. There is now increasing interest in discovering small chemical compounds that can inhibit DNA repair enzymes to reduce the resistance of cells to therapeutic agents. We have recently identified a small molecule that inhibits a DNA repair enzyme called polynucleotide kinase/phosphatase and shown that it enhances the sensitivity of cells to radiation and several important anticancer drugs. The work proposed in this application is directed towards synthesizing, testing and patenting more effective derivatives of the original compound.