Novel approach to treating cancer

by Cesar Chelala

The discovery that two new drugs can control melanoma could revolutionize the treatment not only of melanoma but also of other cancers as well.

Melanoma is cancer of the pigment cells in the skin. Although it accounts for only 4 percent of all skin cancers, it is responsible for almost 80 percent of the deaths, particularly because it tends to spread early in its course.

Melanoma kills by spreading through blood and lymph nodes into the internal organs of the body. This is what makes it more dangerous than other skin cancers, which don’t metastasize as easily.

A melanoma the size of a dime on the skin has a 50 percent chance of having already spread. In addition, melanoma is spreading faster than any other kind of cancer in the United States. It is estimated that at least one person in the country dies of skin cancer every hour.

One study focused on an experimental drug Vemurafenib. It was given to 675 people worldwide with late-stage metastatic melanoma. The drug acts by targeting a mutated gene — carried by 50 percent of melanoma patients — that tell cancer cells to grow rapidly. In patients with this mutation, the drug not only killed cancer cells but also shrank tumor size.

And Vemurafenib, which is taken orally, produces fewer side effects than traditional chemotherapy.

Tumors result from cell growth that gets out of control. Those patients who were responsive to Vemurafenib had a mutation in the “BRAF” gene. The mutation causes production of a protein that triggers rapid cell growth to form tumors. Vemurafenib acts by neutralizing the effects of the mutation in the BRAF gene.

What makes this finding particularly important is that a similar approach may be tried with other cancers whose origins can be traced to a genetic mutation.

The role of the BRAF mutation in the production of melanoma was discovered in 2002 by scientists at the Sanger Institute in Britain. Since then, in Britain and in the U.S., research has focused on whether drugs targeting the mutation might interfere with tumor growth. Although initial trials were disappointing, a new formulation of the drug under study increased penetration of target cells for better results. Prior to this study there were no treatment options for dealing with metastatic melanoma resulting from the BRAF mutation.

“Until now, available therapies [for metastatic melanoma] were few and unreliable, so these findings can really change the outlook for patients whose tumors are fueled by this mutation,” said Keith Flaherty, M.D., director of development therapeutics at the Massachusetts General Hospital Cancer Center and author of the article describing the effects of the new drug.

In a second study, a drug called Ipilimumab, sold under the trade name Yervoy, was tested for its effects on advanced-stage melanoma patients. Yervoy acts differently from Vemurafenib in that it does not target cancer cells but instead stimulates the patients’ immune system response.

The study with this drug showed that 21 percent of patients treated with Yervoy were alive after three years compared to 12 percent of patients who had received traditional chemotherapy or a placebo.

Because Ipilimumab acts by stimulating the patients’ immune system it has been observed to produce serious side effects, including liver damage.

A disadvantage in the use of both drugs is the elevated cost of treatment. However, given the promising results so far, efforts are under way to observe the effects of both drugs used in the same patients.

If initial results are improved, we may be facing a radically new and effective treatment not only of melanoma but of other cancers as well.

Cesar Chelala, M.D., an international public health consultant, conducted research in molecular genetics at the Public Health Institute of the City of New York.