Avoiding Drug Resistance in Melanoma

An anti-cancer drug called vemurafenib is used to combat skin cancers called melanomas. However, in a number of cases, doctors have observed that the drug, which is sold under the name Zelboraf, becomes less effective over time. The drug works by triggering a process called apoptosis, or cell death, in the tumor, and after enough time the drug stops causing apoptosis. A protein in the melanoma becomes active and allows the cancer to survive the onslaught. Last year, researchers found a way to inhibit this protein. Now a different team believe they have found a simpler—and rather counter-intuitive—method to restore the cancer’s vulnerability to the drug.

Melanoma is both the most typical and most serious type of skin cancer, the one associated with tanning beds and other forms of long-term exposure to concentrations of ultraviolet light. A particularly aggressive form of skin cancer, it strikes about 75,000 Americans every year, and is on the rise in people under 40. There are things other than UV light that can cause the genetic damage that results in melanoma. However, frequent sunburn is a risk factor for the illness, as is fair skin. A family history of skin cancer is also a risk factor, suggesting a hereditary component. About 8,000 people die of melanoma every year in the United States, in part because melanoma is among the types of cancer most prone to spread to other parts of the body.

The progression of melanoma is tied to a gene known as BRAF, which is also associated with lung and thyroid cancers. When vemurafenib is administered, it inhibits the effect of this gene, which is important in cell growth. When its activity is blocked, it cannot be used by the tumor cells to grow, and they start to die off, shrinking the tumor.

However, what the researchers found is that the medication not only stops attacking the tumor, but the tumor can start to thrive on it, and harnessing the drug to produce even more of the protein that the BRAF gene is instrumental in building. The solution, they say, is to start and stop the drug regimen. Instead of giving patients the medication straight through until the cancer is gone, they suggest stopping as soon as the tumor has come to depend on the drug, letting it further shrink as its supply is cut off, and resuming, if necessary, only after this cycle has been run through.

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