Ann Arbor, MI — October 29, 2014 — A $1.5 million award from the Prostate Cancer Foundation will fund a team of researchers from the University of Michigan School of Dentistry and their colleagues at Johns Hopkins University to conduct clinical trials to treat metastatic prostate cancer. The award was presented during the Foundation’s 21st annual scientific retreat Oct. 23 in LaCosta, California.
The clinical trials will be led by Dr. Kenneth Pienta, a professor of oncology at the Johns Hopkins University School of Medicine and past director of the Prostate Specialized Program of Research Excellence (SPORE) at the University of Michigan from 1995-2013. During his time at U-M, Pienta collaborated extensively with Dr. Russell Taichman, associate dean for research and professor in the Department of Periodontics and Oral Medicine at the School of Dentistry. Their prostate cancer research collaboration continues.
Taichman’s team in Ann Arbor and Pienta’s team in Baltimore have been investigating possible interrelationships in stem cell development, cancer cell proliferation and bone biology. Taichman, the Major Ash Collegiate Professor of Dentistry, has been investigating the mechanisms which regulate bone metastasis of prostate and other cancers with skeletal structures.
Their research revealed that the bone marrow and the blood stem cell niche play a central role in bone metastasis (cancers that spread into bone). They discovered that when cancer cells invade the bone marrow, the cancer cells and hematopoietic stem cells (cells that give rise to all blood cells) often compete for the same space.
When metastatic prostate cancer cells compete with hematopoietic stem cells in the bone marrow, the cancer cells often become dormant, sometimes for as long as ten years. When this happens, men treated for prostate cancer using a combination of surgery and chemotherapy are often believed to be cancer free. However, many patients later learn their cancer has metastasized and is now incurable.
“In the blood stem cell niche, cancer cells cannot be killed. However, we believe that those outside the niche can be destroyed,” Taichman said. “Since prostate cancer cells frequently metastasize to the bones, we want to find ways to coax cancer cells out of the marrow so they can be targeted using existing chemotherapies.”
That effort will involve a small-scale clinical trial testing two drugs on men with prostate cancer to see if two drugs can coax the tumor cells out of the bone marrow. “If the cancer cells are dormant, we may be able to flush them out of the marrow by interfering with how they bind to the bone marrow and move them into an area where chemotherapeutic drugs might be able to eradicate them,” Taichman said.
The two potential drugs that may be used in the clinical trial are Neupogen and AMD3100. Neupogen (filgrastim) is often used to prevent infection and fevers resulting from chemotherapy. AMD3100 (plerixafor) is a drug that may also fight cancer by releasing tumor cells out of the bone marrow and into the bloodstream. Both drugs, Taichman said, have been approved for use in humans by the Food and Drug Administration. In combination with chemotherapy, Neupogen or AMD3100 may prove safe and effective for treatment of metastatic prostate cancer.
“We have used both drugs in animal models and have had favorable results,” Taichman said. “Our next step is a small-scale clinical trial to see if one or both of these may help patients with prostate cancer.”
Taichman’s U-M research team includes Matthew Eber, Janice Berry, and Drs. Younghun Jung Yusuke Shiozawa. Other project collaborators were: Dr. Richard Jones, director of the Bone Marrow Transplant Program at Johns Hopkins School of Medicine, and Dr. Michael Schweizer, assistant professor at the University of Washington School of Medicine.