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 microenvironment. Specifically, she has designed pro-drug compounds containing "triggers" that are activated by either the hypoxic environment or by high levels of hydrogen peroxide deep inside a tumor. The hypoxia responsive anti-tumor compounds can also be activated specifically in tumors using ionizing radiation. 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, colon cancer, or renal cancer cell lines.
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) and solid cancer tumors have been widely shown to be low in oxygen or hypoxic in nature. Previous attempts at creating pro-drugs activated under hypoxic conditions depended on the presence of enzymes and cofactors, the levels of which are often very low in necrotic tumor tissue. The use of radiation-inducible hypoxia responsive triggers coupled to multiple effectors for the generation of more potent anticancer pro-drugs is novel. Furthermore, Dr. Peng's ROS-activated triggers provide a new alternative for clinical use. These pro-drugs are designed to undergo tumor-specific activation to release DNA inter-strand cross-links which are deleterious to 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 microenvironment.
In the last decade, oncology has been one of the largest segments in the pharmaceutical market, with a major focus on targeted agents specific to tumors. Cancer is one of the fastest growing markets at $80 billion per year. The NIH estimates that the overall costs of cancer in 2010 were approximately $264 billion. In 2011, about 1.6 million new cancer cases are expected to be diagnosed and almost 600,000 Americans are expected to die of cancer. Cancer is the second most common cause of death in the US, only exceeded by heart disease, accounting for nearly 1 in every 4 deaths. This technology may be widely applicable to all solid tumor types that exhibit hypoxia or increased levels of oxidative stress.
Dr. Xiaohua Peng is an Assistant Professor in the Department of Chemistry and Biochemistry at the University of Wisconsin-Milwaukee. She received her Ph.D. 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.
For further information please contact:
Jessica Silvaggi, Ph.D.
UWM Research Foundation
1440 East North Avenue
Milwaukee, WI 53202
Please reference: OTT ID. 1277
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.