OU College of Medicine Researcher Earns Federal Grant to Study Molecule’s Potential as Cancer Drug Target

The tragic irony about breast cancer is that patients usually don’t die because of the initial tumor, but when the cancer metastasizes.

That reality drives researchers to find a way to keep cancer from spreading. Ralf Janknecht, Ph.D., a researcher in the Department of Cell Biology at the OU College of Medicine, has been analyzing the behavior of a particular molecule that is over produced in breast cancer. This year, he was awarded a five-year, $1.78 million grant from the National Cancer Institute to further evaluate the molecule’s potential in reducing cancer metastasis. His discoveries thus far suggest that the molecule, called DNPH1, has the capability to serve as a drug target for stopping the spread of cancer.

Janknecht has been investigating DNPH1 for many years. His interest was piqued when he discovered that the molecule was being produced in excess in breast cancer, including the major types, HER2-positive, estrogen-positive and triple-negative. He also saw that the amount of DNPH1 correlated with the aggressiveness of the disease – the higher the level of the molecule, the lower the survival rate of the patient.

“That suggested to us that DNPH1 is important for disease initiation and progression, and therefore it could be a new drug target,” he said.
To better understand the role of DNPH1, Janknecht’s laboratory first created a mouse research model in which the molecule was removed. To his surprise, its removal had no effect on the health of the mouse. That was good news because it indicates that higher doses of chemotherapy targeting DNPH1 could be given without normal cells being affected and, therefore, without undesirable side effects. But more study was needed. His next step was to create a mouse model that develops breast cancer and has had the DNPH1 molecule removed. That’s when Janknecht received even better news.

“With the DNPH1 removed, we saw fewer tumors per mouse and a tenfold reduction in metastasis,” he said.

Janknecht’s new grant will allow him to further study why DNPH1’s overproduction leads to more aggressive cancer. As he continues adding to the scientific literature with his research, his aim is to work toward a grant that would allow drug development to begin. The process of research isn’t fast, but its measured progress is important to build a strong foundation of knowledge.

Janknecht’s research also serves as an example of the importance of local funding to keep a project alive. Before he secured his recent federal grant, he was supported by grants from the Presbyterian Health Foundation, the Oklahoma Center for the Advancement of Science and Technology, and the Oklahoma Center for Adult Stem Cell Research, a program of TSET. With the progress he made using those grants, he successfully attracted federal funding.

Learning more about how molecules operate is fascinating as a basic science researcher, Janknecht said, but his determination also is fueled by potentially helping people survive cancer.

“When your motivation is to help cure a disease, you know your research is not only for the books, it’s for real life,” he said. “That’s great motivation.”