New Therapies for Treating Advanced Melanoma
Research presented at the American Academy of Dermatology’s 70th Annual Meeting
While melanoma, the most serious form of skin cancer, is highly curable when detected and treated early, the same is not true for more advanced cases of melanoma – particularly when the disease has spread to lymph nodes or other areas of the body.
Recently, two new drugs approved by the U.S. Food and Drug Administration (vemurafenib and ipilimumab) that target the genetic makeup of melanoma are showing promise in slowing the progression of this disease and, in some cases, extending survival in people with advanced melanoma.
Research shows that certain melanomas have specific genetic abnormalities within the melanoma cells. With targeted therapy, the abnormal gene responsible for these melanomas is targeted in an attempt to undo the damage it is causing the cells. Darrell S. Rigel, MD, FAAD, clinical professor in the department of Dermatology at NYU Langone Medical Center in New York, NY, notes that while a number of targets have been identified, a gene known as BRAF is mutated in 40 to 80 percent of melanoma cells. This mutation causes the cells to grow uncontrollably and cancer to form.
When a BRAF mutation is present, a pathway known as the MAP Kinase Pathway essentially gets “stuck” in the “on” position, and the cells start growing very rapidly. The drug vemurafenib attacks the switch of this pathway (or blocks the “on” switch) so that the cells don’t continue to grow uncontrollably. If effective, the cancer is prevented from getting worse.
With targeted therapy, the abnormal gene responsible for these melanomas is targeted in an attempt to undo the damage it is causing the cells.
While not a cure for melanoma, researchers found during clinical trials that on average, participants who responded to vemurafenib lived more than six months without the melanoma getting worse.
In some studies, it was found that within six to ten months on average, the melanoma cells develop resistance to the drug. In this case, melanoma cells either develop other Kinase proteins to sidestep the pathway, or they simply use another pathway that is not currently active. Either way, they activate to make cells continue to grow.
This new targeted therapy blocks a specific molecule, which may allow the body to recognize, target, and attack melanoma cells. Researchers now are looking at using ipilimumab in combination with vemurafenib, as they each block two different pathways, with the theory that there is less chance for resistance to occur.
While not a cure for melanoma, researchers found during clinical trials that the participants who received only ipilimumab and responded to it lived about 10 months longer. For a few of those given ipilimumab, the results were dramatic. Some have had no signs of cancer for as long as six years.
Dr. Rigel cautions that people taking vemurafenib or ipilimumab may experience troublesome side effects and should be closely monitored by their dermatologist. Studies show that significant rashes have been reported in approximately 40 percent of people using vemurafenib. One-third of those taking vemurafenib developed multiple, aggressive squamous cell carcinomas (another common type of skin cancer).
Advice from the American
Academy of Dermatology
“Before vemurafenib and ipilimumab were introduced, beating advanced melanoma used to be virtually hopeless, and now there is at least some hope for these patients,” says Dr. Rigel. “Targeted therapy is still in its infancy, but already it has been successful in some cases of advanced melanoma. The technique shows that it will work, and I expect we’ll see even more effective treatments in the future as we fine- tune our targeting of melanoma.”
The Academy urges everyone to examine their skin regularly. This means looking over your entire body, including your back, scalp, palms, the soles of your feet, and between your toes. If you notice a mole different from others, or which changes, itches, or bleeds, even if it is smaller than six millimeters, you should make an appointment to see a dermatologist.
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