Researchers from Pitt’s School of Medicine and the National Cancer Institute discovered a… Researchers from Pitt’s School of Medicine and the National Cancer Institute discovered a molecule that protects healthy tissue from radiation damage while making tumor cells more sensitive to radiation.

Dr. Jeffrey Isenberg, a principal investigator in Pitt’s Vascular Medicine Institute, and David D. Roberts, of the National Cancer Institute’s Center for Cancer Research, a part of the National Institutes of Health, co-authored a paper that was published Oct. 21 in Science Translational Medicine.

This is a promising potential cancer treatment. Radiation is used in cancer treatment to kill tumor cells. However, radiation dosage must be limited because radiation also kills normal tissue. This causes side effects like nausea, vomiting, weakness and fatigue. Long-term exposure can lead to scarring and death of normal tissue.

Isenberg’s and Roberts’ two labs collaborated in researching a cell-signaling pathway that influences the body’s response to radiation. They developed a therapy that blocks a molecule called thrombospondin-1 from binding to its receptor, called CD47.

The therapy has been effective in cancer-bearing mouse models, as well as in human cells. It has two benefits that make it a promising cancer treatment. First, it renders radiation less toxic to normal tissue. Thus, higher doses of radiation can be administered with lesser side effects. Second, it makes cancer cells more sensitive to the toxic affects of radiation. Therefore radiation is more effective.

“If one was being seen and evaluated and proceeding through a course of radiation treatment for cancer, this therapy would be an ideal agent to incorporate and allow enhanced dosage levels, probably, of radiation and minimizing the non-specific injury to normal structures and maximizing tumor killing,” Isenberg said.

Isenberg explained that, under normal circumstances, tumors are invaded by immune cells. Radiation damages both cancer cells and immune cells. However, with this new treatment, normal immune cells have resistance to the effects of radiation. Therefore, after radiation, the immune cells have not been disabled. They can invade the cancer and destroy it. So patients have the benefit of radiation that kills cancer cells, plus the added benefit of preserved immune cells that invade the cancer and continue to fight it.

Isenberg said that a potential treatment would not have to be administered on the location of the tumor. Patients could receive an injection before undergoing radiation. Additionally, a single dose is effective, so patients would not need long-term treatments. This minimizes potential side effects of long-term drug treatment.

“Our new science will explore just how high we can go with radiation,” Isenberg said.

In experimental models, researchers saw dramatic improvement with five- or six-fold greater levels of radiation than is normally used. Investigators will need to also explore the toxicology and long-term side effects of the therapy before it can be clinically tested.

However, this therapy does not just offer benefits to cancer patients. The treatment has potential applications for people who have undergone accidental radiation exposure in the nuclear energy field, aerospace and the military in connection with bioterrorism.

“If one were in an area where radiation was used for peaceful purposes, such as energy generation or other things, this would be a potential agent to have around for accidents, and the same for military personnel,” Isenberg said.

This allows the University to position itself for funding from pharmaceutical and radiation imaging companies, as well as military or federal funding.