Radiation damage is one of the most frightening aspects of catastrophic nuclear events but, more often, cancer patients suffer the gut-wrenching side effects of the radiation that is administered in an effort to kill the tumor and save the life. In what one scientist describes as his “eureka moment,” a new drug was envisioned that has turned into a very viable potential weapon in the fights against both cancer and nuclear emergency.
Andrei Gudkov, affiliated with the Roswell Park Cancer Institute, has developed CBLB502, the code name for his new drug that protects healthy cells from the damage caused by radiation even while killing off the cancerous cells. The eureka moment came when he got the idea to put one of cancer’s own sneaky little tricks to work against it.
The trick is apoptosis, or cellular suicide. When healthy cells are exposed to radiation, even at doses that produce damage than can be repaired, they instead do what seems to be suicide. The cells in the bone marrow and gastrointestinal (GI) tract are particularly vulnerable.
Cancer cells, however, use various means of blocking apoptosis, enabling cancerous tumors to grow. One way they block cellular suicide is by activating a signaling pathway known as NFKB, or nuclear factor-KappaB.
By imitating this tumor trick, Gudkov and his team of colleagues were able to block apoptosis in healthy tissue by introducing flagellin, a protein made from bacteria in the GI tract, to activate the NFKB pathway.
They then administered their flagellin-based experimental drug on rhesus monkeys and mice before exposing the animals to full-body, lethal doses of radiation, similar to what might be received during a widespread nuclear emergency. The drug was administered 15 minutes to one hour before radiation exposure.
The remarkable result of this experimental trickery was protection of the animals’ bone marrow and GI tracts from destruction typically caused by radiation, and with no no observable side effects. What is even more exciting is that the cancerous tumors were killed, as desired, by the radiation treatment.
When mice were given the flagellin-based drug an hour after receiving rather high doses of radiation, their survival rate improved although the tissue protection wasn’t as dramatic as when it is administered beforehand.
Gudkov has founded a company, Cleveland Biolabs Inc., with the goal of bringing the drug to market. He intends it to be used in both cancer radiation therapies and for biodefense means. The US Department of Defense is one of several government agencies providing funds for the research.