Dr. Xiaohua Peng has used a synergistic combination of synthetic chemistry and biological techniques for the development of new anticancer agents that target the tumor micro environment. Specifically, she has designed pro-drug compounds containing “triggers” that are activated by high levels of hydrogen peroxide deep inside a tumor. The compounds contain multiple potent effectors, some of which have been designed to cause DNA damage within the tumor leading to cell death. Several of these compounds have undergone initial testing through the National Cancer Institute’s NCI 60-Cell Line Screen, and show promise in causing cell growth inhibition or death in Leukemia, Non-Small Cell Lung Cancer, and breast cancer. In vitro cytotoxicity assays with H2O2 inducible compounds have shown growth inhibition of cancer cells at less than 1 micromolar and they induced apoptosis in primary leukemic lymphocytes. A nude mouse xenograft trial for breast cancer showed significant decreases in tumor size in treated mice.
Cancer therapies are often as toxic to healthy cells as to cancer cells. A major focus in the development of new therapeutics is to exploit differences in cancer cells so that therapies can be highly targeted to avoid unwanted side effects. Cancer cells are known to exhibit increased intrinsic oxidative stress such as hydrogen peroxide. Dr. Peng’s ROSactivated triggers provide a new alternative for clinical use. These pro-drugs are designed to undergo tumor specific activation to release compounds that cause DNA inter-strand cross-links, which are deleterious to cancer cells because they block DNA replication and transcription. These compounds are ideal for cancer treatment due to their lack of toxicity in the body until they are located within the tumor micro environment.
United States Utility Patent, Anti-Cancer Agents: 8,962,670
This technology is part of an active and ongoing research program and is seeking partners for development of the final product. It is available for developmental research support/licensing under either exclusive or non-exclusive terms.
Xiaohua Peng, Yunyan Kuang, Sheng Cao, Yibin Wang
Dr. Xiaohua Peng is an Associate Professor in the Department of Chemistry and Biochemistry at the University of Wisconsin-Milwaukee. She received her PhD from the University of Osnabrueck in Germany from Department of Biochemistry. She conducted Post-doctoral research at Johns Hopkins University. Her research interests include the design and synthesis of new antitumor, anticancer, and antiviral agents and the production of mechanistic probes for studying DNA damage.