2010-072 – Novel Bifunctional Cancer Drugs

BackgroundMost cancer chemotherapy and radiation therapy kills cancer cells by damaging their DNA and preventing DNA replication. Cancer cells resist therapy and relapse by increasing their ability to repair their DNA and then proceed to replicate their DNA. Identifying the DNA repair proteins that cancer cells use to repair their DNA after therapy would provide new targets to enhance therapy and prevent relapse. Small chemical inhibitors of those target DNA repair and replication proteins could prevent cancer cells from escaping therapy. It has been demonstrated that Metnase is important for DNA repair, and it is required for DNA replication fork re-start after stalling. Replication forks can stall at sites of cross-linked DNA. By connecting a potent Metnase inhibitor with a nitrogen mustard DNA alkylating agent, a drug can be created that would be much more difficult for cancer cells to deal with. In one molecule DNA is cross-linked by the nitrogen mustard group, which would stall replication forks, and at the same time, Metnase is inhibited, which is required to re-start stalled replication forks. This would inhibit the very mechanism by which the cell would deal with the cross linked DNA. Technology Description University of New Mexico researchers have developed novel cancer treatment compositions. The invention particularly relates to small chemical bifunctional inhibitors of DNA replication and repair proteins Metnase and/or Intnase that simultaneously damage DNA, and to a therapeutic method that utilizes the inhibitors to increase the effectiveness of cancer treatment protocols, especially for leukemia. Gregg Banninger GBanninger@innovations.unm.edu 505-272-7908