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Oct. 2, 2015

Two common medicines found to fight deadly childhood cancer

A combination of two medicines long used for treating other illnesses can stop the growth of a deadly childhood cancer, according to a recent study by a Michigan State University College of Human Medicine researcher who has a history of finding new uses for old drugs.

Laboratory tests on cell cultures showed that the drugs DFMO and sulfasalazine effectively impeded the growth of neuroblastoma, which causes about 15 percent of all childhood cancer deaths.

For years DFMO, or difluoromethylornithine, has been used for treating African sleeping sickness, and sulfasalazine for bowel disorders and rheumatoid arthritis.

“It’s such a big advantage when you find an existing, FDA-approved drug that acts on neuroblastoma, because it already has been shown to be safe,” said André Bachmann, lead author of the study, which was published in the medical journal BMC Cancer.

Separately, each drug impeded neuroblastoma in laboratory tests, but when administered together, the two drugs acted synergistically and were more than twice as effective in blocking the cancer’s growth.

“Instead of one plus one equals two, it equals four,” Bachmann said, who is also a professor of pediatrics and associate chair for research in the College of Human Medicine’s Department of Pediatrics and Human Development. “That’s why the synergistic effect is so important. We can use the two drugs in lower doses, thus achieving the same result while minimizing side effects.”

Each year, about 700 children in this country, most of them age 2 and younger, are diagnosed with neuroblastoma, a highly aggressive tumor, which forms on nerve cells in several areas of the body. With current treatments, neuroblastoma usually goes into remission, but returns in about half of those cases. Only about 10 percent of children with recurring neuroblastoma survive.

Bachmann’s earlier research has shown that DFMO targets a protein called ornithine decarboxylase, or ODC, which when elevated in the cancer, promotes the growth of neuroblastoma cells.

“In this most recent study, we were interested in finding a second drug that would work even better in combination with DFMO,” Bachmann said.

He began the search and learned that other recent studies had shown that the drug sulfasalazine blocked a second protein called sepiapterin reductase, or SPR, which also promotes the growth of neuroblastoma. Sulfasalazine has long been used in treating inflammatory bowel diseases, Crohn’s disease, and rheumatoid arthritis.

“That’s what’s very exciting about this drug,” Bachmann said. “I’m very confident about this, because it’s a safe drug that has been taken by humans for many years with little side effects.”

Bachmann collaborated with other researchers, including Lisette Yco, a graduate student in his Grand Rapids laboratory, and with Dirk Geerts, a cancer researcher in the Netherlands and anticipates this safe drug combination will soon be evaluated in clinical trials.