An arthritis drug may one day also serve as a new treatment for patients with melanoma that has started to spread throughout their body, according to a new study.
The results show leflunomide, a drug used to treat rheumatoid arthritis, can restrict the growth of malignant melanoma tumors in mice, the researchers say.
And when leflunomide was given in combination with another potential melanoma treatment, a drug called PLX4720, it could completely prevent tumor growth, said study researcher Grant Wheeler, a developmental biologist at the University of East Anglia in the United Kingdom.
If the same effect is seen in people, the drug might be used along with chemotherapy to prevent melanomas from coming back, Wheeler said. Patients with malignant melanoma frequently see their tumors return after they have had surgery to remove them, he said.
Since leflunomide is already approved for use in humans, a clinical trial testing the drug in melanoma patients could begin quite soon, within the next six months, Wheeler said. And a treatment might be available in five years, he said.
"Melanoma is one of those cancers which up to now has been very resistant to treatment of any kind," Wheeler said. "With the identification of this compound, we've got something now which hopefully will provide a really useful treatment in the very near future," he said.
The results will be published March 24 in the journal Nature.
Preventing melanoma
Melanoma is the deadliest form of skin cancer, killing about 8,700 people in the United States each year, according to the National Cancer Institute. While overall cancer death rates declined by 19 percent in men and 11 percent in women between 1991 and 2005, the death rate for melanoma increased by 5 percent. [Why Skin Cancer Is on the Rise]
Melanoma is a cancer of pigment cells. The researchers screened 2,000 compounds, looking for those that affect the development of pigment cells in zebrafish and tadpoles.
The development of organisms from an egg to a multicellular creature is a very controlled process, Wheeler said — the opposite of cancer in which cells proliferate uncontrollably. "Many of the genes that are involved in development quite often are mutated in cancer," Wheeler said.
This screening turned up leflunomide as a potential candidate, which the team tested on mice that had been injected with human melanoma cells.
The drug may work by turning off genes involved in cell growth, Wheeler said.
The BRAF mutation
The drug was only tested on melanomas that have a mutation in a gene called BRAF. About 50 percent of patients with melanoma have tumors with the BRAF mutation.
"It would be interesting to see the effects of leflunomide on melanomas that do not have BRAF mutations and to understand if there are synergistic effects when used with other treatment options," said Mary Hendrix, of Northwestern University Feinberg School of Medicine in Chicago, who was not involved in the current study.
While there are drugs available to treat melanomas with the BRAF mutation, known as BRAF inhibitors, "nearly every patient treated with the BRAF inhibitor has become resistant," said Keiran Smalley, of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla., who wasn't part of the current study.
The authors suggest leflunomide might be used in combination with BRAF inhibitors to overcome resistance, but more studies are needed to show this potential, Smalley said. In the study, animals were only treated with [the] drug for relatively short periods of time … and this is probably too early for resistance to have actually emerged," he said.
In addition, leflunomide is known to suppress the immune system, which can increase the risk of cancer, Smalley said.
But experts agree the new study has provided significant insights into the biology of melanoma.
"To describe all of this in the context of one study is something of a tour de force," Smalley said.
Pass it on: The drug leflunomide may inhibit the growth of melanoma when used in combination with other treatments. Clinical trials still need to be conducted to see whether the drug works in people.
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