Researchers from the University of East Anglia (UEA) in the United Kingdom reveal how adding leflunomide — an immunosuppressive drug used for treating rheumatoid arthritis — to a current melanoma treatment halted the growth of melanoma cancer cells in mice.
The team's promising findings were recently published in the journal Oncotarget.
Melanoma is a form of skin cancer that begins in melanocytes, which are skin cells that produce melanin — that is, the pigment that helps to protect our skin from the sun, and which gives the skin its "tan" color.
According to the American Cancer Society (ACS), melanoma accounts for just 1 percent of all skin cancers, but it is responsible for a large proportion of skin cancer deaths.
This year alone, around 9,730 people in the United States are expected to die from melanoma, highlighting the need for more effective treatments.
Lead researcher of the new study Dr. Grant Wheeler, of the School of Biological Sciences at UEA, and colleagues believe that leflunomide could help to meet this need by boosting existing melanoma treatments.
Leflunomide triggers apoptosis
The fact that leflunomide is an immunosuppressive drug is important. "With melanoma treatments," Dr. Wheeler explains, "the main problem has been the development of tumor resistance. One way this is being combatted is through immunotherapy treatments which harness the body's own defenses."
"However," he adds, "new combination therapies are always needed and we need to identify new drugs that can be added to the arsenal of anti-melanoma therapies available for patients."
To see whether leflunomide might be a suitable candidate, the researchers first tested the drug on melanoma cells in the laboratory.
They discovered that the drug was able to halt the early phase of melanoma cell growth, before forcing the melanoma cells into programmed cell death, or apoptosis, a self-destruction process that cancer cells often manage to evade.
The team then tested leflunomide on melanoma cells in combination with selumetinib, which is a drug already used for the treatment of melanoma. Selumetinib works by inhibiting the activity of MEK, a protein that aids the survival of melanoma cells.
The researchers found that the leflunomide-selumetinib combination was more effective for halting melanoma cell growth than leflunomide or selumetinib alone.
Drug combination halted tumor growth
Next, the scientists tested the combination of leflunomide and selumetinib on mice with melanoma tumors and compared its effects with each of these drugs alone.
The team found that the leflunomide-selumetinib combination successfully halted melanoma tumor growth and reduced tumor size in the rodents within 12 days. This treatment was significantly more effective than treatment with each drug individually.
Further explaining the results, the researchers say:
"[...] when leflunomide and selumetinib was administered in combination, the tumor volume not only decreased to levels significantly smaller than either drug treatment alone, but importantly tumor growth was suppressed, with tumor volumes remaining steady at the same size over the 12-day treatment period."
Based on their findings, Dr. Wheeler and colleagues believe that leflunomide has the potential to improve current treatments for the most deadly form of skin cancer. However, further studies are needed to confirm whether this goal can be achieved.
"Future work will determine the mechanism of drug synergy afforded by combined treatment of melanoma cells with leflunomide and selumetinib," say the researchers.
"Furthermore, additional preclinical experiments are needed to determine if melanoma cells can acquire resistance to leflunomide and whether the drug could also be successfully used in combination with anti-melanoma immunotherapies."