Prostate Cancer Drug Could Protect Bone Marrow from Damage Caused by Radiation

Cross sections of mouse femurs showing bone marrow after radiation and no drug (left) and after radiation plus drug (right).

The two cross sections of mouse femurs above show the bone marrow after radiation exposure (left) and after radiation that is followed by a prostate cancer drug given 24 hours later (right). The bone marrow on the left is greatly depleted of blood cells, while the one on the right shows blood cell recovery.

Damage to the bone marrow is a common side effect of radiation exposure — either from cancer treatment or an accidental exposure. Given that the bone marrow is the source of new blood cells, including the white blood cells that provide immunity, people with damaged bone marrow are at risk for life-threatening infections and other complications.

Researchers at Memorial Sloan Kettering, in collaboration with the Fred Hutchinson Cancer Research Center, have identified a potential new way to protect bone marrow cells from radiation-induced damage and promote blood cell recovery after a radiation injury. A team of scientists led by Marcel van den Brink, Head of the Division of Hematologic Oncology and Co-Director of the Parker Institute for Cancer Immunotherapy at MSK, and Jarrod Dudakov, assistant member at Fred Hutch, found that blocking the action of a hormone called luteinizing-hormone releasing hormone (LHRH) could dramatically improve survival in mice that received an otherwise lethal dose of radiation.

“Giving the mice a single dose of the LHRH-blocking drug 24 hours after the radiation hit was enough to protect them from its lethal effects,” says Enrico Velardi, a scientist in the van den Brink lab and the first author of the new study.

LHRH is produced by the brain’s hypothalamus and sets in motion a chain of events that leads to the production of sex hormones in the body. The LHRH-blocking drug lowers the levels of an intermediate step in this chain called luteinizing hormone (LH). The scientists discovered that blood stem cells in the bone marrow respond to LH by dividing. Following an insult to the bone marrow, such as radiation exposure, inhibiting LH prevents cells from proliferating thus maintaining them in a more quiescent state. This dormancy protects blood stem cells from radiation damage and allows them to replenish the blood supply after the injury.

If everything works out, this could be a really feasible way to promote blood cell recovery in people exposed to radiation.
Enrico Velardi research associate

LH also triggers the gonads to make sex hormones, like testosterone and estrogen. Previous studies by Dr. van den Brink and others, including Richard Boyd, who trained Dr. Dudakov, showed that testosterone had important effects in regulating recovery of blood cells after injury. Here, the researchers found that the effect of the drug on survival in the mice was not dependent upon changes in the levels of these hormones. The study provides clear evidence that LH itself can directly regulate hematopoiesis (the production of new blood cells).

While there is still a long way to go before these findings can be translated into a real therapy, there is reason to be optimistic. The LHRH-blocking drug used in this study is already FDA approved to treat men with prostate cancer, so its safety, side effects, and effective dosage are all well known.

“If everything works out, this could be a really feasible way to promote blood cell recovery in people exposed to radiation — including from a worst-case scenario such as a nuclear accident or a terrorist attack,” Dr. Velardi says.

A paper describing the research appears today in Nature Medicine.

This research was supported by the National Institutes of Health, the Lymphoma Foundation, the Susan and Peter Solomon Divisional Genomics Program, Cycle for Survival, the European Union’s Seventh Programme, the Parker Institute for Cancer Immunotherapy at MSK, the Italian Foundation for Cancer Research, the Italian Society of Pharmacology, the American Society of Bone Marrow Transplantation, the Australian National Health and Medical Research Council, the American Society of Hematology, the DKMS Foundation for Giving Life, and Boehringer Ingelheim Fonds. The authors have filed provisional patent applications related to this work.