Dr. Cher and research associate Dr. Jeffrey Nemeth try to stop prostate cancer from harming the bones, where it can cause great pain, fractures and paralysis.

Compared with other cancers, prostate cancer has a marked propensity to spread, or metastasize, to the bones. Men who die of prostate cancer do so after the disease has spread to the skeleton, said Michael Cher, MD, assistant professor of urology and pathology and a member of the Center for Molecular Medicine and Genetics. Once the cancer spreads to the bones, it becomes much more difficult to treat and impossible to cure.

The United States Department of Defense Prostate Cancer Research Program awarded Dr. Cher $557,000 to study gene therapy treatments to halt prostate cancer growth in the bones. Preliminary investigations, funded with seed money from Wayne State University and the Barbara Ann Karmanos Cancer Institute, allowed Dr. Cher to develop a mouse-human model which successfully mimics human prostate cancer bone metastasis.

“Human bones are implanted in the mouse, and a few weeks later, human prostate cancer cells are injected. Just as in our patients, the cancer cells seek out and attack the bone,” said Dr. Cher. “In addition, we found that the human prostate cancer cells grow better in the human bone than in any other human or mouse tissue.”

Prostate cancer patients suffer from bone pain and abnormal bone fractures due to the destructive effect of prostate cancer cells on bone. Dr. Cher and his research associate, Dr. Jeffrey Nemeth, found that this destruction of bone structure is caused by a group of proteins called matrix metalloproteinases (MMPs) that are able to digest tissue. In bone biopsies from prostate cancer patients and in bone tumors in the animal model, Dr. Cher and Dr. Nemeth found a sharp increase in MMP activity, leading them to look for ways to block MMPs, and perhaps inhibit cancer growth.

Through genetic manipulation, Dr. Cher and Dr. Nemeth are trying to program the bone cells to secrete TIMPs, a group of proteins that inhibit MMP activity. “We are training the human bone cells to create a hostile environment that will reject the cancer cells and suppress cancer growth,” he said. If this strategy is successful in the animal model, the investigations could move into clinical trials.

“Hormone treatment has traditionally been used to halt cancer in the bones. And although it may put the cancer in remission for a brief time, it always ultimately fails,” said Dr. Cher. Inadequate treatment modalities have contributed to prostate cancer becoming the second leading cause of cancer death in men, with lung cancer being the first.

“I’m hoping that we can advance to the point where we can inject genetically modified bone cells into patients with prostate cancer bone metastases, thereby inhibiting cancer growth and increasing our likelihood of treating bone metastases before complications develop.”