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Arthritis Drug Could Thwart Melanoma: Study

March 24, 2011

A breakthrough discovery may offer an effective new treatment for melanoma, one of the deadliest forms of skin cancer, scientists said on Wednesday.

The researchers found that leflunomide – a drug commonly used to treat rheumatoid arthritis ““ also inhibits the growth of malignant melanoma.  Furthermore, when leflunomide was used in combination with PLX4720, a promising new melanoma therapy currently undergoing clinical trials, the effect was even more powerful ““ leading to a nearly complete block of tumor growth.

Leflunomide was initially sold under the brand name Arava by Sanofi-Aventis, but is now sold generically.

If further trials prove successful — both for leflunomide alone and in combination with Roche and Plexxikon’s PLX4032 — patients could have access to new treatments in three to five years, said the scientists from Britain’s University of East Anglia (UEA) and Children’s Hospital Boston.

Japanese drugmaker Daiichi Sankyo acquired Plexxikon for $805 million in March.

“This is a really exciting discovery — making use of an existing drug specifically to target melanoma,” said researcher Grant Wheeler of the UEA.

Melanoma is a cancer of the pigment cells in our skin, and is the most aggressive form of skin cancer.  If caught early, surgery can be used to safely remove the tumor.  However, if the cancer returns and spreads there are virtually no good alternative treatments and the chances of survival are very low. Conventional chemotherapy typically works in only 10 to 20 percent of these cases.

Unlike most other cancers, the incidence of melanoma is increasing.

In the current research, scientists began examining the effects of various chemical compounds on pigments in frogs and zebrafish in a screening process.

“Cancer is a disease not only of genetic mutations, but also one determined by the identity of the cell in which the tumor arises. By studying cancer development in zebrafish and frogs, we gain a unique insight into the very earliest changes that occur in those cells,” said lead author Dr. Richard White of Children’s Hospital Boston and Harvard Medical School.

The results of the screening process eventually led the researchers to test the drug leflunomide in mice engrafted with human melanoma cells.

After observing that the drug slowed the growth of these tumors, they combined it with Roche and Plexxikon’s drug — a so-called BRAF inhibitor known as PLX4720.

“We thought combining that drug, which targets a specific oncogenic mutation, with leflunomide, which changes the cell’s lineage, could have a beneficial effect,” said Leonard Zon, one of the research team leaders from Children’s Hospital Boston.

The results proved Zon correct. Compared with each drug alone, the combination led to a dramatic decrease in melanoma, and even with low doses of each drug the tumors went away completely in 40 percent of the mice, the researchers said.

The results mean that human trials could start within the next six months, since the safety of both drugs has already been established, the researchers said.

“Deaths from melanoma skin cancer are increasing and there’s a desperate need for new, more effective treatments,” Wheeler told Reuters.

“If this does what we think it will and we find patients are responding to it in the trials, then it could be being used in patients in three to five years.”

Interestingly, some of genes that leflunomide pauses are those controlled by myc, a well known oncogene implicated in several cancer types, the researchers said.

The studies appear in the March 24, 2011, issue of the journal Nature. 

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