Often what kills cancer patients is not the cancer at its original or primary site, but its spread to secondary sites within the body, through a process called metastasis. In the case of breast cancer, the tumor often spreads to the bone, and it is this bone metastasis that results in intense pain and precedes the cancer’s spread to other organs.

In an effort to combat metastatic breast cancer, the U.S. Department of Defense has jointly awarded a $6.7 million grant to Huntsman Cancer Institute (HCI) at the University of Utah, and the Translational Genomics Research Institute (TGen), an affiliate of City of Hope.

With this new funding, HCI will focus on the biology of an important cellular pathway in metastatic breast cancer, while TGen will focus on drug development and supervise clinical trials to test those drugs.

“This is a critical unmet medical need. Cancer that has spread to the bone can cause unbearable pain for these patients,” said Dr. Jeffrey Trent, TGen President and Research Director. “For the first time, this team’s novel approach will seek to uncover this hidden cancer and enlist an immune response while at the same time preventing further damage to skeletal structures.”

A target protein, called RON kinase, was discovered by HCI investigators to support the growth of metastatic breast cancer, but also suppresses the body’s own anti-tumor immune responses.

We found that this protein, RON kinase, plays a very critical role in influencing the surrounding immune cells in the bone environment, suppressing the natural anti-tumor immune response, and thereby facilitating metastatic growth of the tumor,” said Dr. Alana Welm, HCI investigator and Associate Professor in the Department of Oncological Sciences at the University of Utah.

Dr. Welm will be the lead researcher for this study at HCI, who last year published a study about the effects of RON kinase in the journal, Science Translational Medicine.

“When breast cancer spreads to the bones, it destroys the bone in a process similar to what happens in osteoporosis, except to a much greater extent,” Dr. Welm explained. “The cancer causes bone to be eaten up. So you quite literally get holes in the skeleton.”

While breast cancer treatment has progressed significantly in recent years, no cure for metastatic breast cancer currently exists. In order for breast cancer to metastasize, cancer cells must be able to escape the primary cancer site, enter into the bloodstream, invade other tissues, modify the new site, and create a new tumor. Nearly three in four metastatic breast cancer patients experience their cancer spreading to the bone, with median survival rate of only two to three years.

“We believe that working on a new approach that can block RON kinase in the bone can also stop metastasis, blocking the deterioration of the bone and enhancing anti-tumor immunity,” said Dr. Sunil Sharma, M.D., TGen Deputy Director and Director of TGen’s Applied Cancer Research and Drug Discovery Division.

Dr. Sharma will supervise drug development at TGen and supervise clinical trials at HonorHealth Cancer Research Institute, where he serves as Chief of Translational Oncology and Drug Development. He also is a Professor of Medicine at City of Hope.

“We’ve identified a novel strategy that blocks the activity of RON kinase in the bone microenvironment. In preliminary studies, we’ve shown it to have potential to advance treatment of bone metastases from breast cancer,” said Dr. Sharma, a former physician-scientist at HCI, whose work complements Dr. Welm’s research.

Dr. Michael Caligiuri, M.D., the immediate past President of the American Association for Cancer Research (AACR) and a renowned physician-scientist, said that finding new ways to prevent breast cancer from spreading could substantially reduce the pain and suffering of breast cancer patients, and their families.

“More than 2.5 million live successfully with breast cancer. I believe this project holds great hope for extending the survival and quality of life for many others,” said Dr. Caligiuri, who is the Deana and Steve Campbell Physician-in-Chief Distinguished Chair and President of City of Hope National Medical Center.

This study is funded by a grant from the Department of Defense Office of the Congressionally Directed Medical Research Programs, whose mission, in part, is to develop, deliver and sustain medical capabilities, and enhance warfighter readiness.